Obesity‐related Polymorphisms and Their Associations With the Ability to Regulate Fat Oxidation in Obese Europeans: The NUGENOB Study |
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| Authors: | Eva Corpeleijn Liselotte Petersen Claus Holst Wim H. Saris Arne Astrup Dominique Langin Ian MacDonald J. Alfredo Martinez Jean‐Michel Oppert Jan Polak Oluf Pedersen Philippe Froguel Peter Arner Thorkild I.A. Sørensen Ellen E. Blaak |
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| Affiliation: | 1. Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands;2. National Centre for Register‐based Research, University of Aarhus, Aarhus, Denmark;3. Institute of Preventive Medicine, Copenhagen University Hospital, Centre for Health and Society, Copenhagen, Denmark;4. Department of Human Nutrition, Centre for Advanced Food Research, The Royal Veterinary and Agricultural University, Copenhagen, Denmark;5. Obesity Research Laboratory, INSERM U858, Louis Bugnard Institute and Clinical Investigation Centre, Toulouse University Hospitals, Paul Sabatier University, Toulouse, France;6. School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Medical School, Nottingham, UK;7. Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain;8. Department of Nutrition, Hotel‐Dieu Hospital (Assistence‐Publique‐H?piteaux de Paris), University Pierre‐et‐Marie Curie (Paris 6), Paris, France;9. Department of Sports Medicine, Centre of Preventive Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic;10. Steno Diabetes Center and Hagedorn Research Institute, Copenhagen, Denmark;11. Institute of Biomedicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark;12. Faculty of Health Science, University of Aarhus, Aarhus, Denmark;13. CNRS UPRES A8090, Institut Biologie de Lille, Institut Pasteur de Lille, Lille, France;14. Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden |
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| Abstract: | Both obesity and insulin resistance have been related to low fat oxidation rates, which may be genetically determined. The association between variation in fat oxidation rates among obese subjects and genotype was studied for 42 common single‐nucleotide polymorphisms (SNPs) in 26 candidate genes for fat oxidation, insulin resistance, and obesity, including FTO. Energy expenditure (EE) and fat oxidation were measured with indirect calorimetry during fasting and 3 h after a high fat load containing 95 energy% of fat (60% saturated fat, energy content 50% of estimated resting EE) in 722 obese subjects (541 women, 181 men) from 8 European centers. After adjustment for center and gender, ?178 A>C CD36 (rs2232169) (P = 0.02), ?22510 C>G SLC6A14 (women, rs2011162) (P = 0.03), and T690S C>G PCSK1 (rs6235) (P = 0.02) were related to a reduced fat oxidation, whereas 17 C>G SREBF1 (17 C>G) (P = 0.01) was related to increased fat oxidation in the fasting state. The ability to increase fat oxidation after a high fat load was increased in subjects with ?174 G>C IL6 (rs1800795) (P = 0.01). Effect sizes range from 1.1 to 3.1% differences in fat oxidation (expressed as % of EE). FTO rs9939609 was not related to fat oxidation. At the same time, the results are not adjusted for multiple testing, thus none of the associations can be considered statistically significant. The results should therefore only be considered as leads to new hypotheses about effects of specific genetic polymorphisms on fasting and postprandial fat oxidation. |
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