Jocken Johan W E, Blaak Ellen E, van der Kallen Carla J H, van Baak Marleen A, Saris Wim H M
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands.
Metabolism. 2008 Mar;57(3):326-32. doi: 10.1016/j.metabol.2007.10.006.
Obesity is associated with blunted beta-adrenoceptor-mediated lipolysis and fat oxidation, which persist after weight reduction. We investigated whether dinucleotide (CA)(n) 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-mediated 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) < or = body mass index < 30 kg/m(2)) and obese (body mass index > or =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 beta-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 i7 and i6 of the HSL gene might be associated with a physiological effect on in vivo beta-adrenoceptor-mediated fat oxidation, at least in overweight-obese female subjects.
肥胖与β-肾上腺素能受体介导的脂肪分解和脂肪氧化减弱有关，且体重减轻后这种情况仍会持续。我们研究了激素敏感性脂肪酶（HSL）基因内含子6（i6）或7（i7）中的二核苷酸（CA）(n)重复多态性以及C-60G启动子替代是否与超重肥胖受试者体内β-肾上腺素能受体介导的循环脂肪酸和甘油增加减弱（脂解反应评估）及脂肪氧化有关。共纳入103名超重（25kg/m²≤体重指数＜30kg/m²）和肥胖（体重指数≥30kg/m²）受试者（62名男性，41名女性）。在逐步输注递增剂量的非选择性β-激动剂异丙肾上腺素后，测定能量消耗、呼吸商（RQ）以及循环脂肪酸和甘油水平。通过大小分辨毛细管电泳测定i6、i7（CA）(n)重复多态性；通过限制性酶切分析测定C-60G启动子替代。β-肾上腺素能受体介导的刺激后，i7等位基因184的女性非携带者（n = 18）和i6等位基因240的女性携带者（n = 12）的脂肪氧化总体降低（以RQ变化表示），分别解释了RQ变异的6.9%和20.8%。在男性受试者中未观察到这些效应。总之，我们的结果表明，HSL基因i7和i6的变异可能与体内β-肾上腺素能受体介导的脂肪氧化的生理效应有关，至少在超重肥胖女性受试者中如此。
