Blunted β-adrenoceptor-mediated fat oxidation in overweight subjects:: a role for the hormone-sensitive lipase gene

Obesity is associated with blunted beta-adrenoceptor-mediated lipolysis and fat oxidation, which persist after weight reduction. We investigated whether dinucleotide (CA),, repeat polymorphisms in intron 6 (i6) or 7 (i7) and a C-60G promoter substitution of the hormone-sensitive lipase (HSL) gene are associated with a blunted in vivo beta-adrenoceptor-rnediated increase In circulating fatty acids and glycerol (estimation of lipolytic response) and fat oxidation in overweight-obese subjects. A total of 103 overweight (25 kg/m(2) <= body mass index < 30 kg/m(2)) and obese (body mass index >= 30 kg/m(2)) subjects (62 men, 41 women) were included. Energy expenditure, respiratory quotient (RQ), and circulating fatty acid and glycerol were determined after stepwise infusion of increasing doses of the nonselective A-agonist isoprenaline. The i6, i7 (CA)(n) repeat polymorphisms were determined by size-resolved capillary electrophoresis; and a C-60G promoter substitution was determined by restriction enzyme digestion assay. Female noncarriers of allele 184 i7 (n = 18) and female carriers of allele 240 i6 (n = 12) showed an overall reduced fat oxidation (as indicated by changes in RQ) after beta-adrenoceptor-mediated stimulation, explaining, respectively, 6.9% and 20.8% of the variance in RQ. These effects were not seen in male subjects. In conclusion, our results suggest that variation in P and i6 of the HSL gene might be associated with a physiological effect on in vivo P-adrenoceptor-mediated fat oxidation, at least in overweight-obese female subjects. (C) 2008 Elsevier Inc. All rights reserved.