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Dietary Fatty Acids, Body Composition and Ectopic Fat : Results from Overfeeding Studies in Humans
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to investigate the effects of dietary fatty acids on body composition and ectopic fat in humans, with emphasis on the role of the omega-6 polyunsaturated fatty acid (PUFA) linoleic acid (18:2n-6) and the saturated fatty acid (SFA) palmitic acid (16:0). The overall hypothesis was that linoleic acid would be beneficial compared with palmitic acid during overfeeding, as previously indicated in animals.

Papers I, II and IV were double-blinded, randomized interventions in which different dietary fats were provided to participants and Paper III was a cross-sectional study in a community-based cohort (PIVUS) in which serum fatty acid composition was assessed as a biomarker of dietary fat intake.

In Paper I, overfeeding with sunflower oil (n-6 PUFA) for 7 weeks caused less accumulation of liver fat, visceral fat and total body fat (as assessed by MRI) compared with palm oil (SFA) in young and lean subjects despite similar weight gain among groups. Instead, sunflower oil caused a larger accumulation of lean tissue.

In Paper II, plasma from Paper I was analyzed with NMR-based metabolomics, aiming to identify metabolites differentially affected by the two dietary treatments. Acetate decreased by PUFA and increased by SFA whereas lactate increased by PUFA and decreased by SFA.

In Paper III, the proportion of linoleic acid in serum was inversely associated with contents of visceral-, subcutaneous- and total body adipose tissue whereas the proportion of palmitic acid was directly associated with visceral- and total body adipose tissue in 70-year old men and women.

In Paper IV, overfeeding with sunflower oil for 8 weeks caused less accumulation of liver fat compared with palm oil also in overweight and obese subjects. SFA increased visceral fat in men only. Accumulation of lean tissue was similar between groups.

In conclusion, SFA (palmitic acid) from palm oil promotes marked liver fat accumulation in both normal-weight and overweight/obese subjects during overeating, whereas n-6 PUFA (linoleic acid) from sunflower oil prevents such liver fat accumulation. Diverging effects of SFA and PUFA on visceral adipose tissue and lean tissue may only be applicable in some groups and/or circumstances. These results imply that negative effects associated with weight gain (e.g. fatty liver) may be partly counteracted by the type fat in the diet, overall supporting a beneficial role of diets higher in unsaturated fat compared with saturated fat for preventing liver fat accumulation. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , p. 94
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1358
Keyword [en]
Linoleic acid, Palmitic acid, SFA, PUFA, Fatty acids, Body composition, Liver fat, Ectopic fat, Adipose tissue
National Category
Nutrition and Dietetics
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-280949ISBN: 978-91-554-9523-7 (print)OAI: oai:DiVA.org:uu-280949DiVA, id: diva2:913391
Public defence
2016-05-13, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2016-04-22 Created: 2016-03-16 Last updated: 2016-04-29
List of papers
1. Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans
Open this publication in new window or tab >>Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans
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2014 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 7, p. 2356-2368Article in journal (Refereed) Published
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.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-223915 (URN)10.2337/db13-1622 (DOI)000337918200025 ()24550191 (PubMedID)
Available from: 2014-04-28 Created: 2014-04-28 Last updated: 2017-12-05Bibliographically approved
2. NMR-based metabolic profiling in healthy individuals overfed different types of fat: links to changes in liver fat accumulation and lean tissue mass.
Open this publication in new window or tab >>NMR-based metabolic profiling in healthy individuals overfed different types of fat: links to changes in liver fat accumulation and lean tissue mass.
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2015 (English)In: Nutrition & Diabetes, ISSN 2044-4052, E-ISSN 2044-4052, Vol. 5, no 19, p. e182-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Overeating different dietary fatty acids influence the amount of liver fat stored during weight gain, however, the mechanisms responsible are unclear. We aimed to identify non-lipid metabolites that may differentiate between saturated (SFA) and polyunsaturated fatty acid (PUFA) overfeeding using a non-targeted metabolomic approach. We also investigated the possible relationships between plasma metabolites and body fat accumulation.

METHODS: In a randomized study (LIPOGAIN study), n=39 healthy individuals were overfed with muffins containing SFA or PUFA. Plasma samples were precipitated with cold acetonitrile and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Pattern recognition techniques were used to overview the data, identify variables contributing to group classification and to correlate metabolites with fat accumulation.

RESULTS: We previously reported that SFA causes a greater accumulation of liver fat, visceral fat and total body fat, whereas lean tissue levels increases less compared with PUFA, despite comparable weight gain. In this study, lactate and acetate were identified as important contributors to group classification between SFA and PUFA (P<0.05). Furthermore, the fat depots (total body fat, visceral adipose tissue and liver fat) and lean tissue correlated (P(corr)>0.5) all with two or more metabolites (for example, branched amino acids, alanine, acetate and lactate). The metabolite composition differed in a manner that may indicate higher insulin sensitivity after a diet with PUFA compared with SFA, but this needs to be confirmed in future studies.

CONCLUSION: A non-lipid metabolic profiling approach only identified a few metabolites that differentiated between SFA and PUFA overfeeding. Whether these metabolite changes are involved in depot-specific fat storage and increased lean tissue mass during overeating needs further investigation.

National Category
Medical and Health Sciences Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-267034 (URN)10.1038/nutd.2015.31 (DOI)000368899900002 ()26479316 (PubMedID)
Funder
Swedish Research Council, K2015-54X-22081-04-3Swedish Diabetes Association
Note

Rosqvist, Engskog, Haglöf, Riséus and Pettersson contributed equally to this work.

Available from: 2015-11-17 Created: 2015-11-17 Last updated: 2017-12-01Bibliographically approved
3. Visceral and subcutaneous adipose tissue content is diversely associated with serum polyunsaturated and saturated fatty acids
Open this publication in new window or tab >>Visceral and subcutaneous adipose tissue content is diversely associated with serum polyunsaturated and saturated fatty acids
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(English)Article in journal (Refereed) Submitted
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-280947 (URN)
Available from: 2016-03-16 Created: 2016-03-16 Last updated: 2016-04-29
4. Effects of overfeeding polyunsaturated and saturated fat on lean tissue, liver fat and visceral fat accumulation in overweight and obese humans
Open this publication in new window or tab >>Effects of overfeeding polyunsaturated and saturated fat on lean tissue, liver fat and visceral fat accumulation in overweight and obese humans
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-280948 (URN)
Available from: 2016-03-16 Created: 2016-03-16 Last updated: 2016-04-29

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