Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation.
OBJECTIVE
Obesity is associated with a blunted beta-adrenoceptor-mediated lipolysis and fat oxidation. We investigated whether polymorphisms in codon 16, 27 and 164 of the beta (2)-adrenoceptor gene (ADRB2) and exon 10 of the G protein beta (3)-subunit gene (GNB3) are associated with alterations in in vivo lipolysis and fat oxidation.


METHODS
Sixty-five male and 43 female overweight and obese subjects (body mass index (BMI) range: 26.1-48.4 kg/m(2)) were included. Energy expenditure (EE), respiratory quotient (RQ), circulating free fatty acid (FFA) and glycerol levels were determined after stepwise infusion of increasing doses of the non-selective beta-agonist isoprenaline (ISO).


RESULTS
In women, the Arg16 allele of the ADRB2 gene was associated with a blunted increase in circulating FFA, glycerol and a decreased fat oxidation during ISO stimulation. In men, the Arg16 allele was significantly associated with a blunted increase in FFA but not in glycerol or fat oxidation.


CONCLUSIONS
These results suggest that genetic variation in the ADRB2 gene is associated with disturbances in in vivo beta-adrenoceptor-mediated lipolysis and fat oxidation during beta-adrenergic stimulation in overweight and obese subjects; these effects are influenced by gene-gender interactions.
Jocken
J W E
JW
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. j.jocken@hb.unimaas.nl
Blaak
E E
EE
Schiffelers
S
S
Arner
P
P
van Baak
M A
MA
Saris
W H M
WH
D000273:Adipose Tissue / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000886:Anthropometry; D004734:Energy Metabolism; D005260:Female; D014644:Genetic Variation; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics*
D000318:Adrenergic beta-Agonists; C454420:G-protein beta3 subunit; D018343:Receptors, Adrenergic, beta-2; D020962:Heterotrimeric GTP-Binding Proteins; D007545:Isoproterenol