Several obesity- and nutrient-related gene polymorphisms but not FTO and UCP variants modulate postabsorptive resting energy expenditure and fat-induced thermogenesis in obese individuals: the NUGENOB study.
BACKGROUND
Part of the heterogeneity of the obesity phenotype may originate from genetic differences between obese individuals that may influence energy expenditure (EE).


OBJECTIVE
To examine if common single-nucleotide polymorphisms (SNPs) in genes related to obesity-associated phenotypes are associated with postabsorptive resting energy expenditure (REE) and postprandial REE in obese individuals.


METHODS
Postabsorptive REE and 3-h postprandial REE (liquid test meal containing 95% fat, energy content 50% of estimated REE) were measured in 743 obese individuals from eight clinical centres in seven European countries. The analysis assessed the association of genotypes of 44 SNPs in 28 obesity-related candidate genes with postabsorptive REE and postprandial REE taking into consideration the influence of body composition, habitual physical activity, insulin sensitivity, circulating thermogenic hormones and metabolites.


RESULTS
After adjustment for fat-free mass (FFM), age, sex and research centre, SNPs in CART, GAD2, PCSK1, PPARG3, HSD11B1 and LIPC were significantly associated with postabsorptive REE. SNPs in GAD2, HSD11B1 and LIPC remained significantly associated with postabsorptive REE after further adjustment for fat mass (FM). SNPs in CART, PPARG2 and IGF2 were significantly associated with postprandial REE after similar adjustments. These associations with postprandial REE remained significant after further adjustment for FM. FTO, UCP2 and UCP3 variants were not associated with postabsorptive or postprandial REE.


CONCLUSIONS
Several gene polymorphisms associated with obesity-related phenotypes but not FTO and UCP variants may be responsible for some of the inter-individual variability in postabsorptive REE and fat-induced thermogenesis unaccounted for by FFM, FM, age and sex. The association between FTO and obesity that has been reported earlier may not be mediated directly through modulation of EE in obese individuals.
Goossens
G H
GH
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. G.Goossens@hb.unimaas.nl
Petersen
L
L
Blaak
E E
EE
Hul
G
G
Arner
P
P
Astrup
A
A
Froguel
P
P
Patel
K
K
Pedersen
O
O
Polak
J
J
Oppert
J-M
JM
Martinez
J A
JA
Sørensen
T I A
TI
Saris
W H M
WH
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics; D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D004734:Energy Metabolism / Q000235:genetics* / Q000502:physiology; D005260:Female; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D008049:Lipase / Q000235:genetics; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019518:Postprandial Period / Q000235:genetics* / Q000502:physiology; D011506:Proteins / Q000235:genetics; D012146:Rest / Q000502:physiology; D022722:Thermogenesis / Q000235:genetics* / Q000502:physiology; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D055815:Young Adult
D007473:Ion Channels; C504173:LIPC protein, human; D024101:Mitochondrial Proteins; D011506:Proteins; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D008049:Lipase; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2