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Mapping the consequenses of physical exercise and nutrition on human health: A predictive metabolomics approach
Umeå University, Faculty of Science and Technology, Department of Chemistry. (Computational Life Science Cluster (CLiC))
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Human health is a complex and wide-ranging subject far beyond nutrition and physical exercise. Still, these factors have a huge impact on global health by their ability to prevent diseases and thus promote health. Thus, to identify health risks and benefits, it is necessary to reveal the underlying mechanisms of nutrition and exercise, which in many cases follows a complex chain of events. As a consequence, current health research is generating massive amounts of data from anthropometric parameters, genes, proteins, small molecules (metabolites) et cetera, with the intent to understand these mechanisms. For the study of health responses, especially related to physical exercise and nutrition, alterations in small molecules (metabolites) are in most cases immediate and located close to the phenotypic level and could therefore provide early signs of metabolic imbalances. Since there are roughly as many different responses to exercise and nutrients as there are humans, this quest is highly multifaceted and will benefit from an interpretation of treatment effects on a general as well as on an individual level. This thesis involves the application of chemometric methods to the study of global metabolic reactions, i.e. metabolomics, in a strategy coined predictive metabolomics. Via the application of predictive metabolomics an extensive hypothesis-free biological interpretation has been carried out of metabolite patterns in blood, acquired using gas chromatography-mass spectrometry (GC-MS), related to physical exercise, nutrition and diet, all in the context of human health. In addition, the chemometrics methodology have computational benefits concerning the extraction of relevant information from information-rich data as well as for interpreting general treatment effects and individual responses, as exemplified throughout this work. Health concerns all lifestages, thus this thesis presents a strategic framework in combination with comprehensive interpretations of metabolite patterns throughout life. This includes a broad range of human studies revealing metabolic patterns related to the impact of physical exercise, macronutrient modulation and different fitness status in young healthy males, short and long term dietary treatments in overweight post menopausal women as well as metabolic responses related to probiotics treatment and early development in infants. As a result, the studies included in the thesis have revealed metabolic patterns potentially indicative of an anti-catabolic response to macronutrients in the early recovery phase following exercise. Moreover, moderate differences in the metabolome associated with cardiorespiratory fitness level were detected, which could be linked to variation in the inflammatory and antioxidaive defense system. This work also highlighted mechanistic information that could be connected to dietary related weight loss in overweight and obese postmenopausal women in relation to short as well as long term dietary effects based on different macronutrient compositions. Finally, alterations were observed in metabolic profiles in relation to probiotics treatment in the second half of infancy, suggesting possible health benefits of probiotics supplementation at an early age.

 

Place, publisher, year, edition, pages
Umeå: Print och Media , 2011. , 60 p.
Keyword [en]
Metabolomics, physical exercise, cardiorespiratory fitness nutrition, high protein and fat diet, Lactobacillus F19, probiotics, GC-MS, plasma, chemometrics, multivariate analysis statistical experimental design, design of experiments
National Category
Other Basic Medicine
Research subject
Systems Analysis; Nutrition; Molecular Medicine
Identifiers
URN: urn:nbn:se:umu:diva-43844ISBN: 978-91-7459-128-6OAI: oai:DiVA.org:umu-43844DiVA: diva2:416489
Public defence
2011-06-03, KB3B1, KBC-huset, Umeå universitet, Umeå, 10:00 (English)
Opponent
Supervisors
Note
Embargo until 2012-06-01Available from: 2011-05-12 Created: 2011-05-12 Last updated: 2011-05-13Bibliographically approved
List of papers
1. A Multivariate Screening Strategy for Investigating Metabolic Effects of Strenuous Physical Exercise in Human Serum
Open this publication in new window or tab >>A Multivariate Screening Strategy for Investigating Metabolic Effects of Strenuous Physical Exercise in Human Serum
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2007 (English)In: Journal of Proteome Research, ISSN 1535-3893, Vol. 6, no 6, 2113-2120 p.Article in journal (Refereed) Published
Abstract [en]

A novel hypothesis-free multivariate screening methodology for the study of human exercise metabolism in blood serum is presented. Serum gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) data was processed using hierarchical multivariate curve resolution (H-MCR), and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to model the systematic variation related to the acute effect of strenuous exercise. Potential metabolic biomarkers were identified using data base comparisons. Extensive validation was carried out including predictive H-MCR, 7-fold full cross-validation, and predictions for the OPLS-DA model, variable permutation for highlighting interesting metabolites, and pairwise t tests for examining the significance of metabolites. The concentration changes of potential biomarkers were verified in the raw GC/TOFMS data. In total, 420 potential metabolites were resolved in the serum samples. On the basis of the relative concentrations of the 420 resolved metabolites, a valid multivariate model for the difference between pre- and post-exercise subjects was obtained. A total of 34 metabolites were highlighted as potential biomarkers, all statistically significant (p < 8.1E-05). As an example, two potential markers were identified as glycerol and asparagine. The concentration changes for these two metabolites were also verified in the raw GC/TOFMS data.The strategy was shown to facilitate interpretation and validation of metabolic interactions in human serum as well as revealing the identity of potential markers for known or novel mechanisms of human exercise physiology. The multivariate way of addressing metabolism studies can help to increase the understanding of the integrative biology behind, as well as unravel new mechanistic explanations in relation to, exercise physiology.

Place, publisher, year, edition, pages
American Chemical Society, 2007
Keyword
Chemometrics, Exercise, GC/MS, Human Metabolism, Metabolomics, Metabonomics, Physiology, Predictive, Screening, Serum
Identifiers
urn:nbn:se:umu:diva-13191 (URN)10.1021/pr070007g (DOI)17428078 (PubMedID)
Available from: 2007-09-28 Created: 2007-09-28 Last updated: 2013-03-19Bibliographically approved
2. A predictive metabolomics evaluation of nutrition-modulated metabolic stress responses in human blood serum during the early recovery phase of strenuous physical exercise
Open this publication in new window or tab >>A predictive metabolomics evaluation of nutrition-modulated metabolic stress responses in human blood serum during the early recovery phase of strenuous physical exercise
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2009 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 8, no 6, 2966-77 p.Article in journal (Refereed) Published
Abstract [en]

We have investigated whether postexercise ingestion of carbohydrates in combination with proteins generates a different systemic metabolic response, as compared to the sole ingestion of carbohydrate or water, in the early recovery phase following exercise. In addition, metabolic patterns related to fitness level were studied together with individual responses to nutritional modulation. Twenty-four male subjects were exposed to 90 min of ergometer-cycling. Each participant was subject to four identical test-sessions, including ingestion of one of four beverages (water, low-carbohydrate beverage, high-carbohydrate beverage, and low-carbohydrate−protein beverage (LCHO-P)) immediately after cycling. Blood was collected at six time points, one pre- and five postexercise. Extracted blood serum was subject to metabolomic characterization by gas chromatography/time-of-flight mass spectrometry (GC−TOF MS). Data was processed using hierarchical multivariate curve resolution (HMCR), and multivariate statistical analysis was carried out using orthogonal partial least-squares (OPLS). Predictive metabolomics, including predictive HMCR and OPLS classification, was applied to ensure efficient sample processing and validation of detected metabolic patterns. Separation of subjects in relation to ingested beverage was detected and interpreted. Pseudouridine was suggested as a novel marker for pro-anabolic effect following LCHO-P ingestion, which was supported by the detected decrease of the catabolic marker 3-methylhistidine. Separation of subjects according to fitness level was achieved, and nutritional modulation by LCHO-P was shown to improve the metabolic status of less fit subjects in the recovery phase. In addition, the potential of the methodology for detection of early signs of insulin resistance was also demonstrated.

Place, publisher, year, edition, pages
Washington: American Chemical Society, 2009
Keyword
GC-MS, metabolomics, predictive metabolomics, chemometrics, human, exercise, serum, recovery, nutrition, pseudouridine
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:umu:diva-21143 (URN)10.1021/pr900081q (DOI)19317510 (PubMedID)
Available from: 2009-04-03 Created: 2009-04-03 Last updated: 2014-11-17Bibliographically approved
3. Physical fitness level is reflected by alterations in the human plasma metabolome
Open this publication in new window or tab >>Physical fitness level is reflected by alterations in the human plasma metabolome
2012 (English)In: Molecular BioSystems, ISSN 1742-206X, Vol. 8, no 4, 1187-1196 p.Article in journal (Refereed) Published
Abstract [en]

An excessive energy intake combined with a low level of physical activity induces detrimental processes involved in disease development, e.g. type 2 diabetes and cardiovascular disease. However the underlying mechanisms for regulation of metabolic capacity and fitness status remain unclear. Metabolomics involves global studies of the metabolic reactions in an organism or cell. Thus hypotheses regarding biochemical events can be generated to increase the understanding of disease development and thereby aid in the development of novel treatments or preventions. We present the first standardized intervention study focusing on characterizing the human metabolome in relation to moderate differences in cardiorespiratory fitness. Gas chromatography-time of flight/mass spectrometry (GC-TOF/MS) was used to characterize 460 plasma samples from 27 individuals divided into two groups based on physical fitness level (VO2max). Multi- and univariate between group comparisons based on 197 metabolites were carried out in samples collected at rest prior to any intervention, over time following a nutritional load or a standardized exercise scheme, with and without nutritional load. We detected decreased levels of gamma-tocopherol (GT), a vitamin E isomer, in response to a high fitness level, whereas the opposite was seen for the alpha isomer (AT). In addition, the high fitness level was associated with elevated ω3-PUFA (DHA, 22:6ω3) and a decrease in ω6-PUFA (18:2ω6) as well as in saturated (16:0, 18:0), monounsaturated (18:1) and trans (16:1) fatty acids. We thus hypothesize that high fitness status induces an increased cardiorespiratory inflammatory and antioxidant defense system, more prone to deal with the inflammatory response following exercise and nutrition intake.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2012
Keyword
Metabolomics, pysical exercise, cardiorespiratory fitness, GC-MS, OPLS and chemometrics
National Category
Biochemistry and Molecular Biology Sport and Fitness Sciences
Research subject
Systems Analysis
Identifiers
urn:nbn:se:umu:diva-43862 (URN)10.1039/C2MB05428K (DOI)
Note

First published on the web 27 Jan 2012

Available from: 2011-05-12 Created: 2011-05-12 Last updated: 2014-11-17Bibliographically approved
4. A metabolomic evaluation of short and long term effects of different macronutrient intake in overweight and obese postmenopausal women
Open this publication in new window or tab >>A metabolomic evaluation of short and long term effects of different macronutrient intake in overweight and obese postmenopausal women
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(English)Manuscript (preprint) (Other academic)
Research subject
Food and Nutrition
Identifiers
urn:nbn:se:umu:diva-43681 (URN)
Available from: 2011-05-05 Created: 2011-05-05 Last updated: 2011-05-18Bibliographically approved
5. The impact of feeding Lactobacillus F19 during weaning: a study of the plasma metabolome
Open this publication in new window or tab >>The impact of feeding Lactobacillus F19 during weaning: a study of the plasma metabolome
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(English)Manuscript (preprint) (Other academic)
Keyword
Metabolomics, probiotics, GC-MS, OPLS and chemometrics
Identifiers
urn:nbn:se:umu:diva-43863 (URN)
Available from: 2011-05-12 Created: 2011-05-12 Last updated: 2011-05-16Bibliographically approved

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