Obesity-related polymorphisms and their associations with the ability to regulate fat oxidation in obese Europeans: the NUGENOB study.
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.
Corpeleijn
Eva
E
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Petersen
Liselotte
L
Holst
Claus
C
Saris
Wim H
WH
Astrup
Arne
A
Langin
Dominique
D
MacDonald
Ian
I
Martinez
J Alfredo
JA
Oppert
Jean-Michel
JM
Polak
Jan
J
Pedersen
Oluf
O
Froguel
Philippe
P
Arner
Peter
P
Sørensen
Thorkild I A
TI
Blaak
Ellen E
EE
D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics; D018955:CD36 Antigens / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005215:Fasting / Q000502:physiology; D005223:Fats / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D015810:Linkage Disequilibrium; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period / Q000502:physiology; D011506:Proteins / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D044465:White People / Q000235:genetics* / Q000706:statistics & numerical data*; D055815:Young Adult
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D018955:CD36 Antigens; D005223:Fats; C508600:IL6 protein, human; D015850:Interleukin-6; D011506:Proteins; C503995:SLC6A14 protein, human; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human