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  • 101. Paniagua, J. A.
    et al.
    Perez-Martinez, P.
    Gjelstad, Ingrid M. F.
    Tierney, Audrey C.
    Delgado-Lista, J.
    Defoort, Catherine
    Blaak, Ellen E.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Drevon, Christian A.
    Kiec-Wilk, Beata
    Lovegrove, Julie A.
    Roche, Helen M.
    Lopez-Miranda, J.
    A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome2011In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 218, no 2, p. 443-450Article in journal (Refereed)
    Abstract [en]

    Objective: Dietary changes are major factor in determining cardiovascular risk. We assessed the effects of isoenergetic diets with different fat quantity and quality on the incidence and regression of the metabolic syndrome (MetS) from the LIPGENE project. Methods and design: Clinical intervention study: the patients (n = 337) were randomly assigned to one of four diets for 12 weeks each: two high fat diets, one rich in saturated fat (HSFA) and the other rich in monounsaturated fat (HMUFA), and two low fat diets, one high in complex carbohydrates (LFHCC) supplemented with 1.24 g/day of long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) and the other LFHCC diet with placebo (LFHCC). Measurements: the effects on MetS risk criteria were recorded before and after the intervention period. Results: An enlarged waist circumference (>= 88 cm for women and >= 102 cm for men) was present among 95% of the participants, 88% had elevated blood pressure (>130/85 mm Hg or antihypertensive drugs), 77% had elevated fasting plasma glucose (>= 5.55 mmol/L), 51% were hypertriacylglycerolemic (>= 1.7 mmol/L), and 72% had low HDL cholesterol (<1.0 mmol/L for men, and <1.3 mmol/L for women). The prevalence of enlarged waist circumference, hypertension and hypertriacylglycerolemia were reduced after the LFHCC n-3 diet (p<0.05). Thus the prevalence of MetS fell by 20.5% after LFHCC n-3 diet compared with the HSFA (10.6%), HMUFA (12%) diet or LFHCC (10.4%) diets (p<0.028). Conclusions: The consumption of a low-fat high-carbohydrate supplemented with n-3 diet reduced the risk of MetS as compared with isoenergetic high-fat (HSFA and HMUFA) and LFHCC diets. 

  • 102.
    Pereira, Maria J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, S.
    AstraZeneca R&D, Molndal, Sweden.;Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Endocrinol, Gothenburg, Sweden..
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sidibeh, Cherno O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Dahgam, S.
    AstraZeneca R&D, Molndal, Sweden..
    Mansson, M.
    AstraZeneca R&D, Molndal, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of free fatty acids in type 2 diabetes2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S323-S323Article in journal (Refereed)
  • 103.
    Pereira, Maria J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Skrtic, Stanko
    AstraZeneca R&D, Molndal, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Endocrinol, Gothenburg, Sweden..
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sidibeh, Cherno O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Dahgam, Santosh
    AstraZeneca R&D, Molndal, Sweden..
    Mansson, Marianne
    AstraZeneca R&D, Molndal, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of NEFA in type 2 diabetes. Degree of hyperglycemia and adiposity are important factors2016In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 65, no 12, p. 1768-1780Article in journal (Refereed)
    Abstract [en]

    Background. Elevated levels of circulating non-esterified fatty acids (NEFA) mediate many adverse metabolic effects. In this work we aim to determine the impact of type 2 diabetes (T2D), glycemic control and obesity on lipolysis regulation. Design and Participants. 20 control and 20 metformin-treated T2D subjects were matched for sex (10 M/10 F), age (58 +/- 11 vs 58 +/- 9 y) and BMI (30.8 +/- 4.6 vs 30.7 +/- 4.9 kg/m(2)). In vivo lipolysis was assessed during a 3 h-OGTT with plasma glycerol and NEFA levels. Subcutaneous adipose tissue (SAT) biopsies were obtained to measure mRNA and metabolite levels of factors related to lipolysis and lipid storage and to assess in vitro lipolysis in isolated subcutaneous adipocytes. Results. Plasma NEFA AUC during the OGTT where higher 30% (P = 0.005) in T2D than in control subjects, but plasma glycerol AUC and subcutaneous adipocyte lipolysis in vitro were similar, suggesting that adipose tissue lipolysis is not altered. Expression in SAT of genes involved in lipid storage (FABP4, DGAT1, FASN) were reduced in T2D subjects compared with controls, but no differences were seen for genes involved in lipolysis. T2D subjects had elevated markers of beta-oxidation, alpha-hydroxybutyrate (1.4-fold, P < 0.01) and p-hydroxybutyrate (1.7-fold, P < 0.05) in plasma. In multivariate analysis, HbA1c, visceral adipose tissue volume and sex (male) were significantly associated with NEFA AUC in T2D subjects. Conclusions. In T2D subjects, NEFA turnover is impaired, but not due to defects in lipolysis or lipid beta-oxidation. Impaired adipose NEFA re-esterification or de novo lipogenesis is likely to contribute to higher NEFA plasma levels in T2D. The data suggest that hyperglycemia and adiposity are important contributing factors for the regulation of plasma NEFA concentrations.

  • 104. Perez-Martinez, Pablo
    et al.
    Garcia-Rios, Antonio
    Delgado-Lista, Javier
    Gjelstad, Ingrid M. F.
    Gibney, James
    Kiec-Wilk, Beata
    Camargo, Antonio
    Helal, Olfa
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Blaak, Ellen E.
    Hall, Wendy
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dembinska-Kiec, Aldona
    Defoort, Catherine
    Saris, Wim H. M.
    Lovegrove, Julie A.
    Drevon, Christian A.
    Roche, Helen M.
    Lopez-Miranda, Jose
    Gene-nutrient interactions on the phosphoenolpyruvate carboxykinase influence insulin sensitivity in metabolic syndrome subjects2013In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 32, no 4, p. 630-635Article in journal (Refereed)
    Abstract [en]

    Background & aims: Genetic background may interact with habitual dietary fat composition, and affect development of the metabolic syndrome (MetS). The phosphoenolpyruvate carboxykinase gene (PCK1) plays a significant role regulating glucose metabolism, and fatty acids are key metabolic regulators, which interact with transcription factors and influence glucose metabolism. We explored genetic variability at the PCK1 gene locus in relation to degree of insulin resistance and plasma fatty acid levels in MetS subjects. Moreover, we analyzed the PCK1 gene expression in the adipose tissue of a subgroup of MetS subjects according to the PCK1 genetic variants. Methods: Insulin sensitivity, insulin secretion, glucose effectiveness, plasma concentrations of C-peptide, fatty acid composition and three PCK1 tag-single nucleotide polymorphisms (SNPs) were determined in 443 MetS participants in the UPGENE cohort. Results: The rs2179706 SNP interacted with plasma concentration of n - 3 polyunsaturated fatty acids (n - 3 PUFA), which were significantly associated with plasma concentrations of fasting insulin, peptide C, and HOMA-IR. Among subjects with n - 3 PUFA levels above the population median, carriers of the C/C genotype exhibited lower plasma concentrations of fasting insulin (P = 0.036) and HOMA-IR (P = 0.019) as compared with C/C carriers with n - 3 PUFA below the median. Moreover, homozygous C/C subjects with n - 3 PUFA levels above the median showed lower plasma concentrations of peptide C as compared to individuals with the T-allele (P = 0.006). Subjects carrying the T-allele showed a lower gene PCK1 expression as compared with carriers of the C/C genotype (P = 0.015). Conclusions: The PCK1 rs2179706 polymorphism interacts with plasma concentration of n - 3 PUFA levels modulating insulin resistance in MetS subjects. 

  • 105.
    Perfilyev, Alexander
    et al.
    Lund Univ, Clin Res Ctr, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci, Malmo, Sweden..
    Dahlman, Ingrid
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Gillberg, Linn
    Rigshosp, Dept Endocrinol, Diabet & Metab, Copenhagen, Denmark..
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Volkov, Petr
    Lund Univ, Clin Res Ctr, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci, Malmo, Sweden..
    Nilsson, Emma
    Lund Univ, Clin Res Ctr, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci, Malmo, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ling, Charlotte
    Lund Univ, Clin Res Ctr, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci, Malmo, Sweden..
    Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial2017In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 105, no 4, p. 991-1000Article in journal (Refereed)
    Abstract [en]

    Background: Dietary fat composition can affect ectopic lipid accumulation and, thereby, insulin resistance. Diets that are high in saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) have different metabolic responses. Objective: We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a randomized trial. Design: We studied the effects of 7 wk of excessive SFA (n = 17) or PUFA (n = 14) intake (+750 kcal/d) on the DNA methylation of similar to 450,000 sites in human subcutaneous adipose tissue. Both diets resulted in similar body weight increases. We also combined the data from the 2 groups to examine the overall effect of overfeeding on the DNA methylation in adipose tissue. Results: The DNA methylation of 4875 Cytosine-phosphate-guanine (CpG) sites was affected differently between the 2 diets. Furthermore, both the SFA and PUFA diets increased the mean degree of DNA methylation in adipose tissue, particularly in promoter regions. However, although the mean methylation was changed in 1797 genes [e.g., alpha-ketoglutarate dependent dioxygenase (FTO), interleukin 6 (IL6), insulin receptor (INSR), neuronal growth regulator 1 (NEGR1), and proopiomelanocortin (POMC)] by PUFAs, only 125 genes [e.g., adiponectin, C1Q and collagen domain containing (ADIPOQ)] were changed by SFA overfeeding. In addition, the SFA diet significantly altered the expression of 28 transcripts [e.g., acyl-CoA oxidase 1 (ACOX1) and FAT atypical cadherin 1 (FAT1)], whereas the PUFA diet did not significantly affect gene expression. When the data from the 2 diet groups were combined, the mean methylation of 1444 genes, including fatty acid binding protein 1 (FABP1), fatty acid binding protein 2 (FABP2), melanocortin 2 receptor (MC2R), MC3R, PPARG coactivator 1 alpha (PPARGC1A), and tumor necrosis factor (TNF), was changed in adipose tissue by overfeeding. Moreover, the baseline DNA methylation of 12 CpG sites that was annotated to 9 genes [e.g., mitogen-activated protein kinase 7 (MAPK7), melanin concentrating hormone receptor 1 (MCHR1), and splicing factor SWAP homolog (SFRS8)] was associated with the degree of weight increase in response to extra energy intake. Conclusions: SFA overfeeding and PUFA overfeeding induce distinct epigenetic changes in human adipose tissue. In addition, we present data that suggest that baseline DNA methylation can predict weight increase in response to overfeeding in humans.

  • 106.
    Peters, Harry P. F.
    et al.
    Unilever Res Labs, Olivier van Noortlaan 120, Vlaardingen, Netherlands.
    Schrauwen, Patrick
    Maastricht Univ, Med Ctr, NUTRIM Sch Nutr & Translat Res Metab, Dept Human Biol, Maastricht, Netherlands.
    Verhoef, Petra
    Unilever Res Labs, Olivier van Noortlaan 120, Vlaardingen, Netherlands.
    Byrne, Christopher D.
    Univ Southampton, Fac Med, Nutr & Metab, Southampton, Hants, England;Univ Hosp Southampton, Southampton Natl Inst Hlth Res, Biomed Res Ctr, Southampton, Hants, England.
    Mela, David J.
    Unilever Res Labs, Olivier van Noortlaan 120, Vlaardingen, Netherlands.
    Pfeiffer, Andreas F. H.
    Charite Univ Med Berlin, Dept Endocrinol Diabet & Nutr, Campus Benjamin Franklin, Berlin, Germany;German Inst Human Nutr, Dept Clin Nutr, Potsdam, Germany;DZD, German Ctr Diabet Res, Neuherberg, Germany.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Rosendaal, Frits R.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Schrauwen-Hinderling, Vera
    Maastricht Univ, Med Ctr, NUTRIM Sch Nutr & Translat Res Metab, Dept Human Biol, Maastricht, Netherlands;Maastricht Univ, Med Ctr, NUTRIM Sch Nutr & Translat Res Metab, Dept Radiol, Maastricht, Netherlands.
    Liver fat: a relevant target for dietary intervention? Summary of a Unilever workshop2017In: Journal of Nutritional Science, ISSN 2048-6790, E-ISSN 2048-6790, Vol. 6, article id e15Article, review/survey (Refereed)
    Abstract [en]

    Currently it is estimated that about 1 billion people globally have non-alcoholic fatty liver disease (NAFLD), a condition in which liver fat exceeds 5 % of liver weight in the absence of significant alcohol intake. Due to the central role of the liver in metabolism, the prevalence of NAFLD is increasing in parallel with the prevalence of obesity, insulin resistance and other risk factors of metabolic diseases. However, the contribution of liver fat to the risk of type 2 diabetes mellitus and CVD, relative to other ectopic fat depots and to other risk markers, is unclear. Various studies have suggested that the accumulation of liver fat can be reduced or prevented via dietary changes. However, the amount of liver fat reduction that would be physiologically relevant, and the timeframes and dose-effect relationships for achieving this through different diet-based approaches, are unclear. Also, it is still uncertain whether the changes in liver fat per se or the associated metabolic changes are relevant. Furthermore, the methods available to measure liver fat, or even individual fatty acids, differ in sensitivity and reliability. The present report summarises key messages of presentations from different experts and related discussions from a workshop intended to capture current views and research gaps relating to the points above.

  • 107.
    Petersson, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Serum fatty acid composition and indices of stearoyl-CoA desaturase activity are associated with systemic inflammation: longitudinal analyses in middle-aged men2008In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 99, no 6, p. 1186-1189Article in journal (Refereed)
    Abstract [en]

    Altered fatty acid (FA) composition is related to insulin resistance and CVD. One possible mediator may be inflammation, but longitudinal data relating FA composition to inflammation taking insulin resistance into account are limited. We investigated the long-term association between FA composition and C-reactive protein (CRP) concentrations in a large population-based cohort study in 767 men followed for 20 years. The association between FA composition in serum cholesteryl esters at age 50 and CRP concentrations at age 70 was investigated using linear regression. In addition, desaturase activities (stearoyl-CoA desaturase-1 (SCD-1), Delta 5- and Delta 6-desaturase) were estimated using FA product-to-precursor ratios. Insulin resistance was measured directly at follow-up by euglycaemic clamp. After adjusting for confounders (smoking, physical activity, alcohol intake, obesity and erythrocyte sedimentation rate) CRP concentrations were inversely associated with the proportion of 18:2n-6 (P=0.002) and positively associated with 16:1n-7 (P=0.008), 18: 1n-9 (P=0.0003), 20:5n-3 (P=0.04) and estimated SCD-1 (P=0.005) and Delta 6-desaturase (P=0.02) activities. After adding insulin resistance to the model, 18: 1n-9, 18:2n-6 and SCD-1 remained significant predictors of CRP. A FA composition indicating low intake of 18:2n-6, high intake of SFA and high SCD-1 activity is, in a Swedish population of middle-aged men, associated with CRP concentrations 20 years later, even independently of obesity and insulin resistance.

  • 108.
    Petersson, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Daryani, Achraf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sagittal abdominal diameter as a marker of inflammation and insulin resistance among immigrant women from the Middle East and native Swedish women: a cross-sectional study2007In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 6, p. 10-Article in journal (Refereed)
    Abstract [en]

    Background

    Immigrant women from the Middle East have elevated risk of cardiovascular disease. Sagittal abdominal diameter (SAD), a simple marker of intra-abdominal fat, predicts insulin resistance and cardiovascular mortality in men. Its usefulness in immigrant women is however unknown. To investigate the predictive role of SAD compared to other anthropometric measures, we examined a random sample of native-Swedes and immigrant women from the Middle East living in Sweden.

    Methods

    157 women participated in the study; 107 immigrants and 50 natives. Anthropometric measurements (SAD, body mass index [BMI], waist circumference [WC] and waist-to-hip ratio [WHR]; all measured in supine position) and cardiovascular risk factors (C-reactive protein [CRP], insulin, glucose, insulin resistance [HOMA-IR], blood pressure and serum lipids) were assessed. The anthropometric measures were compared in their relation to cardiovascular risk factors using linear regression analyses.

    Results

    Overall, SAD showed a slightly higher correlation with most cardiovascular risk factors, especially insulin resistance, insulin, CRP, apolipoprotein B and triglycerides (all P-values < 0.01) than other anthropometric measures. BMI was however a better predictor of HDL cholesterol. SAD explained a greater proportion of the variation of insulin resistance and CRP levels, even independently of the other anthropometric measures.

    Conclusion

    SAD identifies insulin resistance, subclinical inflammation or raised serum lipids in a Swedish population with a large proportion of immigrant women from the Middle East. If these results could be confirmed in a larger population, SAD could be a more clinically useful risk marker than other anthropometric measures in women at high risk of cardiovascular disease.

  • 109.
    Petrus, P
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Huddinge, Sweden.
    Edholm, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dahlman, I
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Huddinge, Sweden.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Arner, P
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Huddinge, Sweden.
    Rydén, M
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Huddinge, Sweden.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Depot-specific differences in fatty acid composition and distinct associations with lipogenic gene expression in abdominal adipose tissue of obese women2017In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, no 8, p. 1295-1298Article in journal (Refereed)
    Abstract [en]

    Cardiometabolic diseases are primarily linked to enlarged visceral adipose tissue (VAT). However, some data suggest heterogeneity within the subcutaneous adipose tissue (SAT) depot with potential metabolic differences between the superficial SAT (sSAT) and deep SAT (dSAT) compartments. We aimed to investigate the heterogeneity of these three depots with regard to fatty acid (FA) composition and gene expression. Adipose tissue biopsies were collected from 75 obese women undergoing laparoscopic gastric bypass surgery. FA composition and gene expression were determined with gas chromatography and quantitative real-time-PCR, respectively. Stearoyl CoA desaturase-1 (SCD-1) activity was estimated by product-to-precursor FA ratios. All polyunsaturated FAs (PUFA) with 20 carbons were consistently lower in VAT than either SAT depots, whereas essential PUFA (linoleic acid, 18:2n-6 and α-linolenic acid, 18:3n-3) were similar between all three depots. Lauric and palmitic acid were higher and lower in VAT, respectively. The SCD-1 product palmitoleic acid as well as estimated SCD-1 activity was higher in VAT than SAT. Overall, there was a distinct association pattern between lipid metabolizing genes and individual FAs in VAT. In conclusion, SAT and VAT are two distinct depots with regard to FA composition and expression of key lipogenic genes. However, the small differences between sSAT and dSAT suggest that FA metabolism of SAT is rather homogenous.

  • 110. Petrus, Paul
    et al.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Edholm, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Mejhert, Niklas
    Arner, Peter
    Dahlman, Ingrid
    Ryden, Mikael
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Saturated fatty acids in human visceral adipose tissue are associated with increased 11-beta-hydroxysteroid-dehydrogenase type 1 expression2015In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 14, article id 42Article in journal (Refereed)
    Abstract [en]

    Background: Visceral fat accumulation is associated with metabolic disease. It is therefore relevant to study factors that regulate adipose tissue distribution. Recent data shows that overeating saturated fatty acids promotes greater visceral fat storage than overeating unsaturated fatty acids. Visceral adiposity is observed in states of hypercortisolism, and the enzyme 11-beta-hydroxysteroid-dehydrogenase type 1 (11 beta-hsd1) is a major regulator of cortisol activity by converting inactive cortisone to cortisol in adipose tissue. We hypothesized that tissue fatty acid composition regulates body fat distribution through local effects on the expression of 11 beta-hsd1 and its corresponding gene (HSD11B1) resulting in altered cortisol activity. Findings: Visceral- and subcutaneous adipose tissue biopsies were collected during Roux-en-Y gastric bypass surgery from 45 obese women (BMI; 41 +/- 4 kg/m(2)). The fatty acid composition of each biopsy was measured and correlated to the mRNA levels of HSD11B1. 11 beta-hsd1 protein levels were determined in a subgroup (n = 12) by western blot analysis. Our main finding was that tissue saturated fatty acids (e.g. palmitate) were associated with increased 11 beta-hsd1 gene- and protein-expression in visceral but not subcutaneous adipose tissue. Conclusions: The present study proposes a link between HSD11B1 and saturated fatty acids in visceral, but not subcutaneous adipose tissue. Nutritional regulation of visceral fat mass through HSD11B1 is of interest for the modulation of metabolic risk and warrants further investigation.

  • 111. Phillips, Catherine M.
    et al.
    Tierney, Audrey C.
    Perez-Martinez, Pablo
    Defoort, Catherine
    Blaak, Ellen E.
    Gjelstad, Ingrid M. F.
    Lopez-Miranda, Jose
    Kiec-Klimczak, Malgorzata
    Malczewska-Malec, Malgorzata
    Drevon, Christian A.
    Hall, Wendy
    Lovegrove, Julie A.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Roche, Helen M.
    Obesity and Body Fat Classification in the Metabolic Syndrome: Impact on Cardiometabolic Risk Metabotype2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 1, p. E154-E161Article in journal (Refereed)
    Abstract [en]

    Objective: Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by BMI and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study). Design and Methods: Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules, and hemostatic factors were determined at baseline and after 12 weeks of four dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA), and two low fat high complex carbohydrate (LFHCC) diets, one supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs)). Results: About 39 and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (>= 30 kg/m(2)) and BF% (>= 25% (men) and >= 35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as nonobese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more proinflammatory (higher C reactive protein (CRP) and leptin), prothrombotic (higher plasminogen activator inhibitor-1 (PAI-1)), proatherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA-IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumor necrosis factor-alpha (TNF-alpha) concentrations were lower post-intervention in NOO individuals compared with OO subjects (P < 0.001). Conclusions: In conclusion, assessing BF% and BMI as part of a metabotype may help to identify individuals at greater cardiometabolic risk than BMI alone.

  • 112.
    Riserus, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Geriatrics.
    Trans fatty acids and insulin resistance.2006In: Atheroscler Suppl, ISSN 1567-5688, Vol. 7, no 2, p. 37-9Article in journal (Refereed)
  • 113.
    Riserus, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Transfetter är inget stort problem i Sverige: Men livsmedelsindustrin bör ta bort dem helt ur sina produkter2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 9, p. 658-659Article in journal (Refereed)
    Abstract [en]

    [Trans fats not a big problem in Sweden. But the food industry should eliminate them completely from all products]

     

  • 114.
    Risérus, U
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Smedman, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Metabolic effects of conjugated linoleic acid in humans: the Swedish experience.2004In: Am J Clin Nutr, ISSN 0002-9165, Vol. 79, no 6 Suppl, p. 1146S-1148SArticle in journal (Refereed)
  • 115.
    Risérus, U
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Arner, P
    Zethelius, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Supplementation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity2004In: Diabetologia, Vol. 47, no 6, p. 1016-1019Article in journal (Refereed)
  • 116.
    Risérus, U
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Effects of cis-9, trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men2004In: Am J Clin Nutr, Vol. 80, no 2, p. 279-283Article in journal (Refereed)
  • 117.
    Risérus, U
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Brismar, K
    Zethelius, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berglund, L
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sagittal abdominal diameter is a strong anthropometric marker of insulin resistance and hyperproinsulinemia in obese men2004In: Diabetes Care, no 27, p. 2041-2046Article in journal (Refereed)
  • 118.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cardiovascular Disease2015In: Nutrition for The Primary Care Provider, S. Karger, 2015, p. 94-99Chapter in book (Refereed)
  • 119.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Fatty acids and insulin sensitivity2008In: Current opinion in clinical nutrition and metabolic care, ISSN 1363-1950, E-ISSN 1473-6519, Vol. 11, no 2, p. 100-105Article in journal (Refereed)
    Abstract [en]

    Purpose of review Given the pathophysiological importance of insulin resistance, the potential impact of dietary fatty acids is highly relevant. The effects of different types of dietary fatty acids on insulin sensitivity in humans are discussed, with focus on recent controlled studies. Recent findings Observational studies assessing fatty acid composition in serum or tissues suggest that insulin resistance is associated with relatively high intakes of saturated fat (e.g. palmitic acid) and low intakes of polyunsaturated fat (e.g. linoleic acid), findings that are supported by recent clinical data. Most controlled studies have hitherto examined the effect of monounsaturated fat on insulin sensitivity, several indicating that it has beneficial effects when substituted for saturated fat. More clinical data comparing n-6 polyunsaturated, monounsaturated and saturated fat are needed to identify the optimal dietary fat composition, especially in patients with insulin resistance/obesity and diabetes. The total fat content of the background diet should also be considered in future studies. Finally, we and others hypothesize that dietary fatty acids may partly mediate their effects on insulin action by regulating the activity of lipogenic enzymes and desaturases. Summary Substituting saturated fat with unsaturated fat seems to have beneficial effects on insulin sensitivity, although the clinical significance of modifying fat quality alone is still unclear.

  • 120.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Healthy Nordic diet and cardiovascular disease2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, no 5, p. 542-544Article in journal (Refereed)
  • 121.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Introduction to a healthy Nordic diet: results from the NORDIET study2015In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 67, p. 52-53Article in journal (Other academic)
  • 122.
    Risérus, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Andersson, Agneta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Hambraeus, Leif
    Karolinska Institutet Stockholm.
    Johansson, Ingegerd
    Umeå Universitet.
    Kost och hälsa: Kostrelaterade symptom och sjukdomar2013In: Näringslära för högskolan: Från grundläggande till avancerad nutrition., Stockholm: Liber AB , 2013, 6, p. 309-360Chapter in book (Other (popular science, discussion, etc.))
  • 123.
    Risérus, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Long-term predictors of insulin resistance: role of lifestyle and metabolic factors in middle-aged men2007In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, no 11, p. 2928-2933Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Predictors of insulin resistance have hitherto only been examined in cross-sectional studies without information on lifestyle factors. Few researchers have measured insulin sensitivity directly and compared different metabolic and lifestyle predictors in a large population. RESEARCH DESIGN AND METHODS: Our aim was to investigate independent long-term predictors of insulin sensitivity in a large population-based sample (the Uppsala Longitudinal Study of Adult Men cohort) of 50-year-old men who underwent a euglycemic clamp 20 years later (n = 770). Subjects with diabetes and treatment of cardiovascular disease at baseline were excluded. In linear regression models, metabolic (BMI, triglycerides, HDL cholesterol, glucose, and blood pressure) and lifestyle factors (physical activity, smoking, saturated fat biomarkers, and socioeconomic status) were independent variables at baseline (age 50 years) and insulin sensitivity-dependent variables at follow-up (age 70 years). A subsample of only normal-weight men from the initial population was also examined (n = 440). RESULTS: BMI was the strongest predictor of insulin sensitivity even after addition of metabolic factors. One SD (+/-2.8) increase in BMI corresponded to a mean 19% decrease in insulin sensitivity. After addition of lifestyle factors, all factors except triglycerides and smoking were significant predictors. BMI remained the strongest predictor (beta = -0.67 [95% CI -0.83 to -0.51], P < 0.0001) followed by physical activity, HDL cholesterol, saturated fat, and socioeconomic status (all P < 0.05). BMI remained the strongest predictor in normal-weight subjects also (P < 0.001). In addition, after adjustment for baseline insulin concentrations, BMI remained the strongest predictor (P < 0.001). CONCLUSIONS: Multiple factors, including novel factors such as saturated fat and socioeconomic status, independently predict insulin sensitivity after 20 years. BMI is, however, the single strongest predictor, even in normal-weight subjects.

  • 124.
    Risérus, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Alcohol intake, insulin resistance, and abdominal obesity in elderly men2007In: Obesity (Silver Spring), ISSN 1930-7381, Vol. 15, no 7, p. 1766-1773Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Moderate and high alcohol intake have been associated with decreased and increased risk of type 2 diabetes, respectively. Insulin resistance, insulin secretion, and abdominal obesity are major predictors of diabetes, but the links with alcohol intake remain contradictory because of limited data. RESEARCH METHODS AND PROCEDURES: In a population-based cohort of 807 men (age, 70 years), we studied whether alcohol intake was related to insulin sensitivity, measured with the gold standard technique (euglycemic clamp), insulin secretion (early insulin response), or adiposity [BMI, waist circumference (WC), waist-to-hip ratio]. Alcohol intake was self-reported (questionnaire) and was assessed from a validated 7-day dietary record. The cross-sectional associations were evaluated using multivariable linear regression, adjusting for smoking, education level, physical activity, dietary total energy intake, hypertension, diabetes, triglycerides, and cholesterol. RESULTS: In multivariable models, self-estimated alcohol intake was not related to insulin sensitivity, early insulin response, or BMI, but was positively related to WC (beta-coefficient, 0.77; 95% confidence interval, 0.15 to 1.39; p=0.02) and waist-to-hip ratio (0.006 [0.002-0.009], p=0.003). The association with WC and waist-to-hip ratio was most pronounced in men in the lowest tertile of BMI. The results using dietary records were similar. DISCUSSION: Evaluated in a large sample in elderly men, neither insulin sensitivity measured by clamp technique nor insulin secretion was significantly associated with alcohol intake. However, high alcohol intake was associated with abdominal obesity, which might explain the higher diabetes risk previously observed in high alcohol consumers.

  • 125.
    Risérus, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Marklund, Matti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Milk fat biomarkers and cardiometabolic disease2017In: Current Opinion in Lipidology, ISSN 0957-9672, E-ISSN 1473-6535, Vol. 28, no 1, p. 46-51Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review Dairy is a major food group with potential impact on cardiometabolic health. Self-reported dairy intake has limitations that can partly be avoided by using biomarkers. This review aims to summarize the evidence of odd-chain saturated fatty acids (OCFAs), that is, pentadecanoic acid (C15 : 0) and heptadecanoic acid (17 : 0), as biomarkers of dairy fat intake. In addition, the associations of OCFA biomarkers with cardiometabolic disease will be overviewed. Recent findings Adipose tissue 15 : 0 is the preferred biomarker but also circulating 15 : 0, and to a weaker extent 17 : 0, reflects both habitual and changes in dairy intake. Whereas results from studies assessing cardiovascular outcomes are inconsistent, OCFA biomarkers are overall associated with lower diabetes risk. Residual confounding should however be considered until interventional data and mechanisms are available. Although OCFA biomarkers mainly reflect dairy fat intake, recently proposed endogenous synthesis and metabolism do motivate further research. Summary Taking into account the study population diet and limitations of OCFA biomarkers, both adipose and circulating levels of 15 : 0, in particular, are useful for estimating total dairy fat intake. OCFA biomarkers are overall not linked to cardiovascular disease risk, but a possible beneficial role of dairy foods in diabetes prevention warrant further study.

  • 126.
    Risérus, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sprecher, Dennis
    Johnson, Tony
    Olson, Eric
    Hirschberg, Sandra
    Liu, Aixue
    Fang, Zeke
    Hegde, Priti
    Richards, Duncan
    Sarov-Blat, Leli
    Strum, Jay C
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Cheeseman, Jane
    Fielding, Barbara A
    Humphreys, Sandy M
    Danoff, Theodore
    Moore, Niall R
    Murgatroyd, Peter
    O'Rahilly, Stephen
    Sutton, Pauline
    Willson, Tim
    Hassall, David
    Frayn, Keith N
    Karpe, Fredrik
    Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men2008In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 57, no 2, p. 332-339Article in journal (Refereed)
    Abstract [en]

    OBJECTIEVE-Pharmacological use of peroxisome proliferator-activated receptor (PPAR)delta agonists and transgenic overexpression of PPAR delta in mice suggest amelioration of features of the metabolic syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize a similar mechanism operates in humans. RESEARCH DESIGN AND METHODS-The PPAR delta agonist (10 mg o.d. GW501516), a comparator PPAR alpha agonist (20 mu g o.d. GW590735)), and placebo were given in a double-blind, randomized, three-parallel group, 2-week study to six healthy moderately overweight subjects in each group. Metabolic evaluation was made before and after treatment including liver fat quantification, fasting blood samples, a 6-h meal tolerance test with stable isotope fatty acids, skeletal muscle biopsy for gene expression, and urinary isoprostanes for global oxidative stress. RESULTS-Treatment with GW501516 showed statistically significant reductions in fasting plasma triglycerides (-30%), apolipoprotein B (-26%), LDL cholesterol (-23%), and insulin (-11%), whereas HDL cholesterol was unchanged. A 20% reduction in liver fat content (P < 0.05) and 30% reduction in urinary isoprostanes (P = 0.01) were also observed. Except for a lowering of triglycerides (-30%, P < 0.05), none of these changes were observed in response to GW590735. The relative proportion of exhaled CO, directly originating from the fat content of the meal was increased (P < 0.05) in response to GW501516, and skeletal muscle expression of carnitine palmitoyl-transferase 1b (CPT1b) was also significantly increased. CONCLUSIONS-The PPAR delta agonist GW501516 reverses multiple abnormalities associated with the metabolic syndrome without increasing oxidative stress. The effect is probably caused by increased fat oxidation in skeletal muscle.

  • 127.
    Rosqvist, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Bjermo, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Fatty acid composition in serum cholesterol esters and phospholipids is linked to visceral and subcutaneous adipose tissue content in elderly individuals: a cross-sectional study2017In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 16, p. 1-10, article id 68Article in journal (Refereed)
    Abstract [en]

    Background: Visceral adipose tissue (VAT) and truncal fat predict cardiometabolic disease. Intervention trials suggest that saturated fatty acids (SFA), e. g. palmitic acid, promote abdominal and liver fat storage whereas polyunsaturated fatty acids (PUFA), e. g. linoleic acid, prevent fat accumulation. Such findings require investigation in population-based studies of older individuals. We aimed to investigate the relationships of serum biomarkers of PUFA intake as well as serum levels of palmitic acid, with abdominal and total adipose tissue content.

    Methods: In a population-based sample of 287 elderly subjects in the PIVUS cohort, we assessed fatty acid composition in serum cholesterol esters (CE) and phospholipids (PL) by gas chromatography and the amount of VAT and abdominal subcutaneous (SAT) adipose tissue by magnetic resonance imaging (MRI), liver fat by MR spectroscopy (MRS), and total body fat, trunk fat and leg fat by dual-energy X-ray absorptiometry (DXA). Insulin resistance was estimated by HOMA-IR.

    Results: VAT and trunk fat showed the strongest correlation with insulin resistance (r = 0.49, P < 0.001). Linoleic acid in both CE and PL was inversely related to all body fat depots (r = -0.24 to -0.33, P < 0.001) including liver fat measured in a sub-group (r = -0.26, P < 0.05, n = 73), whereas n-3 PUFA showed weak inverse (18: 3n-3) or positive (20: 5n-3) associations. Palmitic acid in CE, but not in PL, was directly correlated with VAT (r = 0.19, P < 0.001) and trunk fat (r = 0.18, P = 0.003). Overall, the significant associations remained after adjusting for energy intake, height, alcohol, sex, smoking, education and physical activity. The inverse correlation between linoleic acid and VAT remained significant after further adjustment for total body fat.

    Conclusions: Serum linoleic acid is inversely related to body fat storage including VAT and trunk fat whereas palmitic acid was less consistently but directly associated, in line with recent feeding studies. Considering the close link between VAT and insulin resistance, a potential preventive role of plant-based PUFA in VAT accumulation warrants further study.

  • 128.
    Rosqvist, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Johansson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Arner, Peter
    Dahlman, Ingrid
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 7, p. 2356-2368Article in journal (Refereed)
    Abstract [en]

    Excess ectopic fat storage is linked to type 2 diabetes. The importance of dietary fat composition for ectopic fat storage in humans is unknown. We investigated liver fat accumulation and body composition during overfeeding saturated (SFA) or polyunsaturated (PUFA) fat. LIPOGAIN was a double-blind, parallel-group, randomized trial. Thirty-nine young and normal-weight individuals were overfed muffins high in SFA (palm oil) or n-6 PUFA (sunflower oil) for 7 weeks. Liver fat, visceral (VAT), subcutaneous abdominal (SAT), and total adipose tissue (TAT), pancreatic fat, and lean tissue was assessed by MRI. Transcriptomics were performed in SAT. Both groups gained similar weight. SFA however markedly increased liver fat compared with PUFA and caused 2-fold larger increase in VAT than PUFA. Conversely, PUFA caused a nearly 3-fold larger increase in lean tissue than SFA. Increase in liver fat directly correlated with changes in plasma SFA and inversely with PUFA. Genes involved in regulating energy dissipation, insulin resistance, body composition and fat cell differentiation in SAT were differentially regulated between diets, and associated with increased PUFA in SAT. In conclusion, overeating SFA promotes hepatic and visceral fat storage whereas excess energy from PUFA may instead promote lean tissue in healthy humans.

  • 129.
    Rosqvist, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Smedman, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindmark-Mansson, Helena
    Paulsson, Marie
    Petrus, Paul
    Straniero, Sara
    Rudling, Mats
    Dahlman, Ingrid
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Potential role of milk fat globule membrane in modulating plasma lipoproteins, gene expression, and cholesterol metabolism in humans: a randomized study2015In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 102, no 1, p. 20-30Article in journal (Refereed)
    Abstract [en]

    Background: Butter is rich in saturated fat [saturated fatty acids (SFAs)] and can increase plasma low density lipoprotein (LDL) cholesterol, which is a major risk factor for cardiovascular disease. However, compared with other dairy foods, butter is low in milk fat globule membrane (MFGM) content, which encloses the fat. We hypothesized that different dairy foods may have distinct effects on plasma lipids because of a varying content of MFGM. Objective: We aimed to investigate whether the effects of milk fat on plasma lipids and cardiometabolic risk markers are modulated by the MFGM content. Design: The study was an 8-wk, single-blind, randomized, controlled isocaloric trial with 2 parallel groups including overweight men and women (n = 57 randomly assigned). For the intervention, subjects consumed 40 g milk fat/d as either whipping cream (MFGM diet) or butter oil (control diet). Intervention foods were matched for total fat, protein, carbohydrates, and calcium. Subjects were discouraged from consuming any other dairy products during the study. Plasma markers of cholesterol absorption and hepatic cholesterol metabolism were assessed together with global gene-expression analyses in peripheral blood mononuclear cells. Results: As expected, the control diet increased plasma lipids, whereas the MFGM diet did not [total cholesterol (+/- SD): +0.30 +/- 0.49 compared with 0.04 +/- 0.49 mmol/L, respectively (P = 0.024); LDL cholesterol: +0.36 +/- 0.50 compared with +0.04 +/- 0.36 mmol/L, respectively (P = 0.024); apolipoprotein B:apolipoprotein A-I ratio: +0.03 +/- 0.09 compared with 0.05 +/- 0.10 mmol/L, respectively (P = 0.007); and non-HDL cholesterol: +0.24 +/- 0.49 compared with 0.14 +/- 0.51 mmol/L, respectively (P = 0.013)]. HDL-cholesterol, triglyceride, sitosterol, lathosterol, campesterol, and proprotein convertase subtilisin/kexin type 9 plasma concentrations and fatty acid compositions did not differ between groups. Nineteen genes were differentially regulated between groups, and these genes were mostly correlated with lipid changes. Conclusions: In contrast to milk fat without MFGM, milk fat enclosed by MFGM does not impair the lipoprotein profile. The mech-anism is not clear although suppressed gene expression by MFGM correlated inversely with plasma lipids. The food matrix should be considered when evaluating cardiovascular aspects of different dairy foods.

  • 130.
    Ruge, Toralph
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden; Karolinska Inst, Dept Med, Stockholm, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA USA.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Circulating endostatin and the incidence of heart failure.2018In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 5, p. 244-249Article in journal (Refereed)
    Abstract [en]

    Objective: Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community.

    Design: We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966; mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men; mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively).

    Results: Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001); ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts.

    Conclusion: Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.

  • 131. Schwab, Ursula
    et al.
    Lauritzen, Lotte
    Tholstrup, Tine
    Haldorssoni, Thorhallur
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Uusitupa, Matti
    Becker, Wulf
    Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer: a systematic review2014In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 58, p. 25145-Article, review/survey (Refereed)
    Abstract [en]

    The effects of both the amount and quality of dietary fat have been studied intensively during the past decades. Previously, low-fat diets were recommended without much attention to the quality of fat, whereas there is general emphasis on the quality of fat in current guidelines. The objective of this systematic review (SR) was to assess the evidence of an effect of the amount and type of dietary fat on body weight (BW), risk factors, and risk of non-communicable diseases, that is, type 2 diabetes (T2DM), cardiovascular diseases (CVD), and cancer in healthy subjects or subjects at risk for these diseases. This work was performed in the process of updating the fourth edition of the Nordic Nutrition Recommendations from 2004. The literature search was performed in October 2010 covering articles published since January 2000. A complementary search was done in February 2012 covering literature until December 2011. Two authors independently selected articles for inclusion from a total of about 16,000 abstracts according to predefined criteria. Randomized controlled trials (RCT) and prospective cohort studies (PCS) were included as well as nested case control studies. A few retrospective case control studies were also included when limited or no data were available from other study types. Altogether 607 articles were quality graded and the observed effects in these papers were summarized. Convincing evidence was found that partial replacement of saturated fat (SFA) with polyunsaturated fat (PUFA) or monounsaturated fat (MUFA) lowers fasting serum/plasma total and LDL cholesterol concentrations. The evidence was probable for a decreasing effect of fish oil on concentration of serum/plasma total triglycerides as compared with MUFA. Beneficial effect of MUFA both on insulin sensitivity and fasting plasma/serum insulin concentration was considered as probable in comparisons of MUFA and carbohydrates versus SFA, whereas no effect was found on fasting glucose concentration in these comparisons. There was probable evidence for a moderate direct association between total fat intake and BW. Furthermore, there was convincing evidence that partial replacement of SFA with PUFA decreases the risk of CVD, especially in men. This finding was supported by an association with biomarkers of PUFA intake; the evidence of a beneficial effect of dietary total PUFA, n-6 PUFA, and linoleic acid (LA) on CVD mortality was limited suggestive. Evidence for a direct association between total fat intake and risk of T2DM was inconclusive, whereas there was limited-suggestive evidence from biomarker studies that LA is inversely associated with the risk of T2DM. However, there was limited-suggestive evidence in biomarker studies that odd-chain SFA found in milk fat and fish may be inversely related to T2DM, but these associations have not been supported by controlled studies. The evidence for an association between dietary n-3 PUFA and T2DM was inconclusive. Evidence for effects of fat on major types of cancer was inconclusive regarding both the amount and quality of dietary fat, except for prostate cancer where there was limited-suggestive evidence for an inverse association with intake of ALA and for ovarian cancer for which there was limited-suggestive evidence for a positive association with intake of SFA. This SR reviewed a large number of studies focusing on several different health outcomes. The time period covered by the search may not have allowed obtaining the full picture of the evidence in all areas covered by this SR. However, several SRs and meta-analyses that covered studies published before year 2000 were evaluated, which adds confidence to the results. Many of the investigated questions remain unresolved, mainly because of few studies on certain outcomes, conflicting results from studies, and lack of high quality-controlled studies. There is thus an evident need of highly controlled RCT and PCS with sufficient number of subjects and long enough duration, specifically regarding the effects of the amount and quality of dietary fat on insulin sensitivity, T2DM, low-grade inflammation, and blood pressure. New metabolic and other potential risk markers and utilization of new methodology in the area of lipid metabolism may provide new insight.

  • 132.
    Skogar, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Holmbäck, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Preserved Fat-Free Mass after Gastric Bypass and Duodenal Switch2017In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 27, no 7, p. 1735-1740Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Concerns for the possibility of an excessive loss of fat-free mass (FFM) and resting metabolic rate (RMR) after bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) and duodenal switch (BPD/DS), have been raised.

    OBJECTIVES: This study aims to examine body composition and RMR in patients after RYGB and BPD/DS and in non-operated controls.

    METHODS: Body composition and RMR were studied with Bod Pod and indirect calorimetry in weight-stable RYGB (n = 15) and BPD/DS patients (n = 12) and compared with non-operated controls (n = 17). All patients were 30-55 years old and weight stable with BMI 28-35 kg/m(2).

    RESULTS: FFM% was 58% (RYGB), 61% (BPD/DS), and 58% (controls). Body composition did not differ after RYGB and BPD/DS compared to controls, despite 27 and 40% total body weight loss, respectively. No difference in RMR or RMR/FFM was observed (1539, 1617, and 1490 kcal/24 h; and 28.9, 28.4, and 28.8 kcal/24 h/kg).

    CONCLUSION: Weight-stable patients with BMI 28-35 kg/m(2) after RYGB and BPD/DS have a body composition and RMR similar to that of non-operated individuals within the same BMI interval.

  • 133.
    Steubl, Dominik
    et al.
    Tech Univ Munich, Klinikum Rechts Isar, Nephrol Abt, Munich, Germany.
    Kumar, Santhosh V
    Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
    Tato, Maia
    Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
    Mulay, Shrikant R
    Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Renders, Lutz
    Tech Univ Munich, Klinikum Rechts Isar, Nephrol Abt, Munich, Germany.
    Heemann, Uwe
    Tech Univ Munich, Klinikum Rechts Isar, Nephrol Abt, Munich, Germany.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Anders, Hans-Joachim
    Klinikum Univ Munchen, Div Renal, Med Klin & Poliklin 4, Campus Innenstadt, Munich, Germany.
    Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43538Article in journal (Refereed)
    Abstract [en]

    Cardiovascular complications determine morbidity/mortality in chronic kidney disease (CKD). We hypothesized that progressive CKD drives the release of cathepsin-S (Cat-S), a cysteine protease that promotes endothelial dysfunction and cardiovascular complications. Therefore, Cat-S, soluble tumor-necrosis-factor receptor (sTNFR) 1/2 and glomerular filtration rate (GFR) were measured in a CKD mouse model, a German CKD-cohort (MCKD, n = 421) and two Swedish community-based cohorts (ULSAM, n = 764 and PIVUS, n = 804). Association between Cat-S and sTNFR1/2/GFR was assessed using multivariable linear regression. In the mouse model, Cat-S and sTNFR1/2 concentrations were increased following the progressive decline of GFR, showing a strong correlation between Cat-S and GFR (r = -0.746, p < 0.001) and Cat-S and sTNFR1/sTNFR2 (r = 0.837/0.916, p < 0.001, respectively). In the human cohorts, an increase of one standard deviation of estimated GFR was associated with a decrease of 1.008 ng/ml (95%-confidence interval (95%-CI) -1.576-(-0.439), p < 0.001) in Cat-S levels in MCKD; in ULSAM and PIVUS, results were similar. In all three cohorts, Cat-S and sTNFR1/sTNFR2 levels were associated in multivariable linear regression (p < 0.001). In conclusion, as GFR declines Cat-S and markers of inflammation-related endothelial dysfunction increase. The present data indicating that Cat-S activity increases with CKD progression suggest that Cat-S might be a therapeutic target to prevent cardiovascular complications in CKD.

  • 134.
    Strandberg, Emelie
    et al.
    Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Edholm, Peter
    Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Ponsot, Elodie
    Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Wahlin-Larsson, Britta
    Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Hellmen, Erik
    Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Nilsson, Andreas
    Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Engfeldt, Peter
    Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kadi, Fawzi
    Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Influence of combined resistance training and healthy diet on muscle mass in healthy elderly women: a randomized controlled trial2015In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 8, p. 918-925Article in journal (Refereed)
    Abstract [en]

    The delivery of efficient nonpharmacological treatment to prevent the loss of muscle mass in older adults is a major challenge, and information on the combined effects of training and diet is particularly important. Here we aimed to evaluate the effects of 24 wk of resistance training combined with a healthy dietary approach (n-6/n-3 ratio < 2) in a population of healthy and physically active older women (65-70 years). The three-armed randomized controlled trial included a resistance training + healthy diet group (RT-HD), a resistance training group (RT), and controls (CON). All subjects included in the study were physically active and had low levels of serum inflammatory markers. In accordance with the dietary goals, the n-6/n-3 ratio dietary intake significantly decreased only in RT-HD by 42%. An increase in 1 repetition maximum in leg extension occurred in RT (+20.4%) and RT-HD (+20.8%), but not in CON. Interestingly, leg lean mass significantly increased only in RT-HD (+1.8%). While there were no changes in serum C-reactive protein and IL-6 levels, a significant decrease in serum level of the pro-inflammatory precursor arachidonic acid (-5.3 +/- 9.4%) together with an increase in serum n-3 docosahexaenoic acid (+8.3%) occurred only in RT-HD. Altogether, this study demonstrates that the effects of resistance training on muscle mass in healthy older adults can be optimized by the adoption of a healthy diet.

  • 135.
    Straniero, S
    et al.
    Karolinska Univ Hosp Huddinge, Dept Med, Stockholm, Sweden.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Edholm, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Rudling, M
    Karolinska Univ Hosp Huddinge, Dept Med, Stockholm, Sweden.
    Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 5, p. 507-517Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver.

    METHODS: Ten morbidly obese women (BMI 42 ± 2.6 kg m(-2) ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low-calorie diet (800-1100 kcal day(-1) ). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty-four nonobese women (BMI <25 kg m(-2) ) served as controls.

    RESULTS: At baseline, synthesis of both BAs and cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low-calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%.

    CONCLUSIONS: The results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies.

  • 136.
    Straniero, S.
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden..
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Edholm, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Rudling, M.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Stockholm, Sweden..
    Increased Bile Acid And Cholesterol Syntheses And PCSK9 In Morbid Obesity Are Rapidly Normalized Following Acute Caloric Restriction2016In: ATHEROSCLEROSIS, ISSN 0021-9150, Vol. 252, p. E94-E95Article in journal (Refereed)
  • 137.
    Sundstrom, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Clinical value of the metabolic syndrome for long term prediction of total and cardiovascular mortality: prospective, population based cohort study2006In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 332, no 7546, p. 878-882Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To find out if the presence of the metabolic syndrome increases the risk of subsequent total and cardiovascular mortality, taking into account established risk factors for cardiovascular disease. DESIGN: Prospective cohort study. SETTING: General population. PARTICIPANTS: A community based sample of 2322 men followed since 1970 for a maximum of 32.7 years, investigated at ages 50 and 70. MAIN OUTCOME MEASURES: The relations of the metabolic syndrome defined by the national cholesterol education programme (NCEP) of the US National Heart, Lung, and Blood Institute or criteria of the World Health Organization (WHO) to subsequent total and cardiovascular mortality. RESULTS: When adding the metabolic syndrome to models with established risk factors for cardiovascular disease (smoking, diabetes, hypertension, and serum cholesterol) at age 50, presence of the metabolic syndrome as defined in the NCEP significantly predicted total and cardiovascular mortality (Cox proportional hazard ratios 1.36, 95% confidence interval 1.17 to 1.58; and 1.59, 1.29 to 1.95, respectively). The metabolic syndrome added prognostic information to that of the established risk factors for cardiovascular disease (likelihood ratio tests, P < 0.0001 for both outcomes). Similar results were obtained in a subsample without diabetes or manifest cardiovascular disease. CONCLUSIONS: In a large, community based sample of middle aged men, the presence of the metabolic syndrome according to the definition of the NCEP gave long term prognostic information regarding total and cardiovascular mortality if the status of established risk factors for cardiovascular disease was known. If confirmed this may indicate clinical value in diagnosing the metabolic syndrome.

  • 138.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vallhagen, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Risk associated with the metabolic syndrome versus the sum of its individual components2006In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 29, no 7, p. 1673-1674Article in journal (Refereed)
  • 139. Svensson, Viktoria
    et al.
    Sobko, Tanja
    Ek, Anna
    Forssén, Michaela
    Ekbom, Kerstin
    Johansson, Elin
    Nowicka, Paulina
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Westerståhl, Maria
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Marcus, Claude
    Obesogenic dietary intake in families with 1-year-old infants at high and low obesity risk based on parental weight status: baseline data from a longitudinal intervention (Early STOPP)2016In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 55, no 2, p. 781-792Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare dietary intake in 1-year-old infants and their parents between families with high and low obesity risk, and to explore associations between infant dietary intake and relative weight.

    METHODS: Baseline analyses of 1-year-old infants (n = 193) and their parents participating in a longitudinal obesity intervention (Early STOPP) were carried out. Dietary intake and diet quality indicators were compared between high- and low-risk families, where obesity risk was based on parental weight status. The odds for high diet quality in relation to parental diet quality were determined. Associations between measured infant relative weight and dietary intake were examined adjusting for obesity risk, socio-demographics, and infant feeding.

    RESULTS: Infant dietary intake did not differ between high- and low-risk families. The parents in high-risk families consumed soft drinks, French fries, and low-fat spread more frequently, and fish and fruits less frequently (p < 0.05) compared to parents in low-risk families. Paternal intake of vegetables and fish increased the odds for children being consumers of vegetables (OR 1.7; 95 % CI 1.0-2.9) and fish, respectively (OR 2.5; 95 % CI 1.4-4.4). Infant relative weight was weakly associated with a high intake of milk cereal drink (r = 0.15; p < 0.05), but not with any other aspect of dietary intake, obesity risk, or early feeding patterns.

    CONCLUSIONS: At the age of one, dietary intake in infants is not associated with family obesity risk, nor with parental obesogenic food intake. Milk cereal drink consumption but no other infant dietary marker reflects relative weight at this young age.

  • 140.
    Tan, Xiao
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lack of association between self-reported insomnia symptoms and clamp-derived insulin sensitivity in elderly men2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 102, p. 256-260Article in journal (Refereed)
    Abstract [en]

    Insomnia-related sleep disruptions, such as short and disturbed sleep, have been tied to systemic insulin resistance in young adult populations. We therefore sought to confirm these findings in a cohort of elderly men. To this aim, we utilized variables from 980 men who participated in the investigation at age 70 of the Uppsala Longitudinal Study of Adult Men. Self-reported insomnia symptoms were assessed by questions about difficulty initiating sleep, early final awakening, and regular use of hypnotics. All participants also underwent the gold standard hyperinsulinemic-euglycemic clamp technique to assess the insulin sensitivity index (M/I). Finally, fasting blood was collected to measure free fatty acids (FFAs) and adiponectin. Differences in blood parameters between men with and those without insomnia were determined by ANCOVA, and were adjusted for lifestyle and cardio-metabolic risk factors. Our analysis yielded no differences in M/I, FFAs, and adiponectin between men with and those without insomnia symptoms. Analyses in non-diabetic and diabetic subsamples confirmed these negative findings. Our cross-sectional results therefore suggest that insomnia symptoms may have a minimal effect, if any, on measures of insulin sensitivity in elderly men. Given the observational design of our study, future studies are needed to determine whether experimental sleep manipulations influence systemic insulin sensitivity in elderly humans, as has previously been shown in young adult populations.

  • 141.
    Thorning, Tanja Kongerslev
    et al.
    Univ Copenhagen, Dept Nutr Exercise & Sports, Copenhagen, Denmark..
    Bertram, Hanne Christine
    Aarhus Univ, Dept Food Sci, Aarslev, Denmark..
    Bonjour, Jean-Philippe
    Univ Hosp & Fac Med, Dept Internal Med, Geneva, Switzerland..
    de Groot, Lisette
    Wageningen Univ, Human Nutr, Wageningen, Netherlands..
    Dupont, Didier
    French Natl Inst Agr Res INRA, Sci & Technol Milk & Eggs, Rennes, France..
    Feeney, Emma
    Univ Coll Dublin, Sci Ctr South, Food Hlth Ireland, Dublin, Ireland..
    Ipsen, Richard
    Univ Copenhagen, Dept Food Sci, Copenhagen, Denmark..
    Lecerf, Jean Michel
    Inst Pasteur, Lille, France..
    Mackie, Alan
    Univ Leeds, Sch Food Sci & Nutr, Leeds, W Yorkshire, England..
    McKinley, Michelle C.
    Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland..
    Michalski, Marie-Caroline
    Univ Claude Bernard Lyon 1, Inst Natl Sci Appl Lyon INSA Lyon, Inst Multidisciplinaire Biochim Lipides IMBI, INRA,Unit Mixte Rech UMR 1397,INSERM,U1060,Cardio, Villeurbanne, France.;Ctr Europeen Nutr & Sante, Ctr Rech Nutr Humaine Rhone Alpes, Oullins, France..
    Remond, Didier
    Univ Auvergne, INRA, Unite Nutr Humaine, UMR 1019, Clermont Ferrand, France..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Soedamah-Muthu, Sabita S.
    Wageningen Univ & Res, Div Human Nutr, Wageningen, Netherlands..
    Tholstrup, Tine
    Univ Copenhagen, Dept Nutr Exercise & Sports, Copenhagen, Denmark..
    Weaver, Connie
    Purdue Univ, Nutr Sci, W Lafayette, IN 47907 USA..
    Astrup, Arne
    Univ Copenhagen, Dept Nutr Exercise & Sports, Copenhagen, Denmark..
    Givens, Ian
    Univ Reading, Inst Food Nutr & Hlth, Reading, Berks, England..
    Whole dairy matrix or single nutrients in assessment of health effects: current evidence and knowledge gaps2017In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 105, no 5, p. 1033-1045Article in journal (Refereed)
    Abstract [en]

    Foods consist of a large number of different nutrients that are contained in a complex structure. The nature of the food structure and the nutrients therein (i.e., the food matrix) will determine the nutrient digestion and absorption, thereby altering the overall nutritional properties of the food. Thus, the food matrix may exhibit a different relation with health indicators compared to single nutrients studied in isolation. The evidence for a dairy matrix effect was presented and discussed by an expert panel at a closed workshop, and the following consensus was reached: 1) Current evidence does not support a positive association between intake of dairy products and risk of cardiovascular disease (i.e., stroke and coronary heart disease) and type 2 diabetes. In contrast, fermented dairy products, such as cheese and yogurt, generally show inverse associations. 2) Intervention studies have indicated that the metabolic effects of whole dairy may be different than those of single dairy constituents when considering the effects on body weight, cardiometabolic disease risk, and bone health. 3) Different dairy products seem to be distinctly linked to health effects and disease risk markers. 4) Different dairy structures and common processing methods may enhance interactions between nutrients in the dairy matrix, which may modify the metabolic effects of dairy consumption. 5) In conclusion, the nutritional values of dairy products should not be considered equivalent to their nutrient contents but, rather, be considered on the basis of the biofunctionality of the nutrients within dairy food structures. 6) Further research on the health effects of whole dairy foods is warranted alongside the more traditional approach of studying the health effects of single nutrients. Future diet assessments and recommendations should carefully consider the evidence of the effects of whole foods alongside the evidence of the effects of individual nutrients. Current knowledge gaps and recommendations for priorities in future research on dairy were identified and presented.

  • 142.
    Titova, Olga E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ax, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dietary intake of eicosapentaenoic and docosahexaenoic acids is linked to gray matter volume and cognitive function in elderly2013In: Age (Omaha), ISSN 0161-9152, E-ISSN 1574-4647, Vol. 35, no 4, p. 1495-1505Article in journal (Refereed)
    Abstract [en]

    In the present study, we tested whether elderly with a high dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) would have higher cognitive test scores and greater brain volume than those with low dietary intake of these fatty acids. Data were obtained from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. The dietary intake of EPA and DHA was determined by a 7-day food protocol in 252 cognitively healthy elderly (122 females) at the age of 70 years. At age 75, participants' global cognitive function was examined, and their brain volumes were measured by magnetic resonance imaging (MRI). Three different multivariate linear regression models were applied to test our hypothesis: model A (adjusted for gender and age), model B (additionally controlled for lifestyle factors, e.g., education), and model C (further controlled for cardiometabolic factors, e.g., systolic blood pressure). We found that the self-reported 7-day dietary intake of EPA and DHA at the age of 70 years was positively associated with global gray matter volume (P < 0.05, except for model C) and increased global cognitive performance score (P < 0.05). However, no significant associations were observed between the dietary intake of EPA and DHA and global white matter, total brain volume, and regional gray matter, respectively. Further, no effects were observed when examining cognitively impaired (n = 27) elderly as separate analyses. These cross-sectional findings suggest that dietary intake of EPA and DHA may be linked to improved cognitive health in late life but must be confirmed in patient studies.

  • 143. Uusitupa, M.
    et al.
    Hermansen, K.
    Savolainen, M. J.
    Schwab, U.
    Kolehmainen, M.
    Brader, L.
    Mortensen, L. S.
    Cloetens, L.
    Johansson-Persson, A.
    Onning, G.
    Landin-Olsson, M.
    Herzig, K. -H
    Hukkanen, J.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Paananen, J.
    Pulkki, K. J.
    Siloaho, M.
    Dragsted, L.
    Barri, T.
    Overvad, K.
    Knudsen, K. E. Bach
    Hedemann, M. S.
    Arner, P.
    Dahlman, I.
    Borge, G. I. A.
    Baardseth, P.
    Ulven, S. M.
    Gunnarsdottir, I.
    Jonsdottir, S.
    Thorsdottir, I.
    Oresic, M.
    Poutanen, K. S.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Akesson, B.
    Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome: a randomized study (SYSDIET)2013In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 274, no 1, p. 52-66Article in journal (Refereed)
    Abstract [en]

    Background Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. Methods We conducted a randomized dietary study lasting for 18-24weeks in individuals with features of metabolic syndrome (mean age 55years, BMI 31.6kgm-2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Results Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmolL-1 95% CI -0.35; -0.01, P=0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P=0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P=0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37ngL-1, P= 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P=0.049) and magnesium (mg, -0.23, -0.41; -0.05, P=0.012) were associated with IL-1 Ra. Conclusions Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

  • 144.
    Vessby, Bengt
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Smedman, Annika
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Risérus, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Basu, Samar
    Conjugated linoleic acid (CLA) reduces body fat and increases lipid peroxidation in humans2000In: Proceedings of ISSFAL, Japan 2000, 2000Conference paper (Refereed)
  • 145. Waikar, Sushrut S
    et al.
    Sabbisetti, Venkata
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Coresh, Josef
    Feldman, Harold I
    Foster, Meredith C
    Fufaa, Gudeta D
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Hsu, Chi-Yuan
    Kimmel, Paul L
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Liu, Yumin
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Liu, Kathleen D
    Mifflin, Theodore E
    Nelson, Robert G
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Vasan, Ramachandran S
    Xie, Dawei
    Zhang, Xiaoming
    Bonventre, Joseph V
    Relationship of proximal tubular injury to chronic kidney disease as assessed by urinary kidney injury molecule-1 in five cohort studies2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, no 9, p. 1460-1470Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The primary biomarkers used to define CKD are serum creatinine and albuminuria. These biomarkers have directed focus on the filtration and barrier functions of the kidney glomerulus even though albuminuria results from tubule dysfunction as well. Given that proximal tubules make up ∼90% of kidney cortical mass, we evaluated whether a sensitive and specific marker of proximal tubule injury, urinary kidney injury molecule-1 (KIM-1), is elevated in individuals with CKD or with risk factors for CKD.

    METHODS: We measured urinary KIM-1 in participants of five cohort studies from the USA and Sweden. Participants had a wide range of kidney function and were racially and ethnically diverse. Multivariable linear regression models were used to test the association of urinary KIM-1 with demographic, clinical and laboratory values.

    RESULTS: In pooled, multivariable-adjusted analyses, log-transformed, creatinine-normalized urinary KIM-1 levels were higher in those with lower eGFR {β = -0.03 per 10 mL/min/1.73 m(2) [95% confidence interval (CI) -0.05 to -0.02]} and greater albuminuria [β = 0.16 per unit of log albumin:creatinine ratio (95% CI 0.15-0.17)]. Urinary KIM-1 levels were higher in current smokers, lower in blacks than nonblacks and lower in users versus nonusers of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

    CONCLUSION: Proximal tubule injury appears to be an integral and measurable element of multiple stages of CKD.

  • 146. Walsh, Marianne C.
    et al.
    McLoughlin, Gerard A.
    Roche, Helen M.
    Ferguson, Jane F.
    Drevon, Christian A.
    Saris, Wim H. M.
    Lovegrove, Julie A.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lopez-Miranda, Jose
    Defoort, Catherine
    Kiec-Wilk, Beata
    Brennan, Lorraine
    Gibney, Michael J.
    Impact of geographical region on urinary metabolomic and plasma fatty acid profiles in subjects with the metabolic syndrome across Europe: the LIPGENE study2014In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 111, no 3, p. 424-431Article in journal (Refereed)
    Abstract [en]

    The application of metabolomics in multi-centre studies is increasing. The aim of the present study was to assess the effects of geographical location on the metabolic profiles of individuals with the metabolic syndrome. Blood and urine samples were collected from 219 adults from seven European centres participating in the LIPGENE project (Diet, genomics and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis). Nutrient intakes, BMI, waist:hip ratio, blood pressure, and plasma glucose, insulin and blood lipid levels were assessed. Plasma fatty acid levels and urine were assessed using a metabolomic technique. The separation of three European geographical groups (NW, northwest; NE, northeast; SW, southwest) was identified using partial least-squares discriminant analysis models for urine ((RX)-X-2: 0.33, Q(2): 0.39) and plasma fatty acid ((RX)-X-2: 032, Q(2): 0.60) data. The NW group was characterised by higher levels of urinary hippurate and N-methylnicotinate. The NE group was characterised by higher levels of urinary creatine and citrate and plasma EPA (20:5 n-3). The SW group was characterised by higher levels of urinary trimethylamine oxide and lower levels of plasma EPA. The indicators of metabolic health appeared to be consistent across the groups. The SW group had higher intakes of total fat and MUFA compared with both the NW and NE groups (P <= 0.001). The NE group had higher intakes of fibre and n-3 and n-6 fatty acids compared with both the NW and SW groups (all P<0.001). It is likely that differences in dietary intakes contributed to the separation of the three groups. Evaluation of geographical factors including diet should be considered in the interpretation of metabolomic data from multi-centre studies.

  • 147.
    Warensjö, E
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Riserus, U
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men.2005In: Diabetologia, ISSN 0012-186X, Vol. 48, no 10, p. 1999-2005Article in journal (Refereed)
  • 148.
    Warensjö, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Polymorphisms in the SCD1 gene: associations with body fat distribution and insulin sensitivity2007In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 15, no 7, p. 1732-1740Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Obesity and insulin resistance are major risk factors for metabolic diseases and are influenced by lifestyle and genetics. The lipogenic enzyme, stearoyl-coenzyme A-desaturase (SCD), is related to obesity. Further, SCD1-deficent mice are protected against obesity and insulin resistance. We hypothesized that genetic polymorphisms in the SCD1 gene would be associated with obesity, insulin sensitivity, and estimated SCD activity in humans.

    RESEARCH METHODS AND PROCEDURES:

    The study population was 1143 elderly Swedish men taking part of a population-based cohort study, the Uppsala Longitudinal Study of Adult Men. Associations between single nucleotide polymorphisms and obesity (waist circumference and BMI), insulin sensitivity (assessed by hyperinsulinemic euglycemic clamp), and estimated SCD activity (fatty acid ratios) were analyzed using linear regression analysis.

    RESULTS:

    Subjects homozygous for the rare alleles of rs10883463, rs7849, rs2167444, and rs508384 had decreased BMI and waist circumference and improved insulin sensitivity. The rare allele of rs7849 demonstrated the strongest effect on both insulin sensitivity [regression coefficient (beta)=1.19, p=0.007] and waist circumference (beta=-4.4, p=0.028), corresponding to 23% higher insulin sensitivity and 4 cm less waist circumference.

    CONCLUSION:

    This study indicates that genetic variations in the SCD1 gene are associated with body fat distribution and insulin sensitivity, results that accord well with animal data. These results need confirmation in other populations with a larger sample size.

  • 149.
    Warensjö, Eva
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Risérus, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Gustafsson, Inga-Britt
    Örebro Universitet/Grythyttan.
    Mohsen, Rawya
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Geriatrik.
    Cederholm, Tommy
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk Nutrition & Metabolism.
    Vessby, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinsik Nutrition och metabolism.
    Rapsolja förändrar desaturasaktivitet jämfört med smörrik kost.2006In: Läkarstämman, Göteborg 2006, 2006Conference paper (Refereed)
  • 150.
    Warensjö, Eva
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Risérus, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Vessby, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Fatty acid composition of serum lipids predict the development of the metabolic syndrome2005Conference paper (Other (popular scientific, debate etc.))
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