Blunted β-adrenoceptor-mediated fat oxidation in overweight subjects:: a role for the hormone-sensitive lipase gene
Blunted β-adrenoceptor-mediated fat oxidation in overweight subjects:: a role for the hormone-sensitive lipase gene
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DOI：
10.1016/j.metabol.2007.10.006
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发表时间：
2008-03-01
影响因子：
9.8
通讯作者：
Saris, Wim H. M.
中科院分区：
文献类型：
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作者：
Jocken, Johan W. E.;Blaak, Ellen E.;Saris, Wim H. M.
肥胖与钝化的β-肾上腺素能受体介导的脂肪分解和脂肪氧化有关，这些在减肥后仍然存在。我们研究了超重肥胖者体内二核苷酸(CA)、内含子6(I6)或7(I7)重复多态和激素敏感脂肪酶(HSL)基因的C-60G启动子替换是否与体内β-肾上腺素受体钝化的循环脂肪酸和甘油增加(脂解反应的估计)和脂肪氧化有关。研究对象包括103名超重(25 kg/m(2)=30 kg/m(2))受试者(男62人，女41人)。递增剂量的非选择性A受体激动剂异丙肾上腺素后，测定能量消耗、呼吸商(RQ)、循环脂肪酸和甘油。大小分辨毛细管电泳法检测I6、I7(CA)(N)重复序列多态性，限制性内切酶分析法检测C-60G启动子替换。女性184I7非携带者(n=18)和240I6女性携带者(n=12)在β受体介导的刺激后，脂肪氧化总体减少(由RQ的变化指示)，分别解释RQ的6.9%和20.8%。这些影响在男性受试者身上看不到。总之，我们的结果提示，至少在超重肥胖的女性受试者中，HSL基因的P和I6的变异可能与体内P-肾上腺素能受体介导的脂肪氧化的生理效应有关。(C)2008 Elsevier Inc.保留所有权利。
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) = 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.