Tchernof A, Starling R D, Turner A, Shuldiner A R, Walston J D, Silver K, Poehlman E T
Department of Medicine, College of Medicine, University of Vermont, Burlington 05405, USA.
Diabetes. 2000 Oct;49(10):1709-13. doi: 10.2337/diabetes.49.10.1709.
Controversy exists regarding the association between the Trp64Arg variant of the beta3-adrenoceptor gene and visceral obesity. The cross-sectional nature of most studies, the modest effect of the variant, and sex or ethnic differences between groups have contributed to discrepancies among investigations. To overcome these confounding factors, we examined the effect of the Trp64Arg variant on total and visceral adipose tissue loss, insulin sensitivity, and cardiovascular disease risk factors in response to weight reduction in obese older women. A total of 24 women (age 57 +/- 4 years), including 1 Trp64Arg homozygote, 10 Trp64Arg heterozygotes, and 13 normal homozygotes, were admitted to a weight reduction program of 13 +/- 3 months, with weight and nutritional intake stabilization established before testing. Total and regional adiposity were measured with dual-energy X-ray absorptiometry and computed tomography, insulin sensitivity was measured by the hyperinsulinemic-euglycemic clamp technique, and a blood lipid profile was obtained. No baseline differences were noted in adiposity measurements, glucose disposal, and lipid profiles among carriers and noncarriers of the variant allele. In response to weight loss, carriers and noncarriers of the Trp64Arg allele had similar reductions in body weight (-16.4 +/- 5.0 vs. -14.1 +/- 6.2 kg, NS) and body fat (-10.0 +/- 5.2 vs. -11.5 +/- 3.9 kg, NS). However, loss of visceral adipose tissue was 43% lower in carriers of the Trp64Arg allele compared with noncarriers (-46 +/- 27 vs. -81 +/- 51 cm2, P = 0.05). Furthermore, there was less improvement in the total cholesterol-to-HDL cholesterol ratio (-0.18 +/- 0.54 vs. -0.72 +/- 0.56, P = 0.04) in carriers compared with noncarriers of the allele. Although glucose disposal improved in both groups, there was no difference in the magnitude of improvement between carriers and noncarriers of the variant allele. In conclusion, older obese women carrying the Trp64Arg beta3-adrenoceptor gene variant have an impaired capacity to lose visceral adipose tissue in response to prolonged caloric restriction. Despite these genetic differences in loss of intraabdominal adipose tissue, improvement in glucose disposal was similar between groups.
β3 - 肾上腺素能受体基因的色氨酸64精氨酸（Trp64Arg）变体与内脏肥胖之间的关联存在争议。大多数研究的横断面性质、该变体的适度效应以及不同组之间的性别或种族差异导致了各研究之间的差异。为了克服这些混杂因素，我们研究了Trp64Arg变体对肥胖老年女性体重减轻时总脂肪组织和内脏脂肪组织减少、胰岛素敏感性以及心血管疾病风险因素的影响。共有24名女性（年龄57±4岁），包括1名Trp64Arg纯合子、10名Trp64Arg杂合子和13名正常纯合子，参加了为期13±3个月的减肥计划，在测试前确定了体重和营养摄入稳定。用双能X线吸收法和计算机断层扫描测量总脂肪量和局部脂肪量，通过高胰岛素 - 正常血糖钳夹技术测量胰岛素敏感性，并获取血脂谱。变体等位基因携带者和非携带者在脂肪量测量、葡萄糖代谢和血脂谱方面未发现基线差异。在体重减轻方面，Trp64Arg等位基因的携带者和非携带者体重下降相似（-16.4±5.0 vs. -14.1±6.2 kg，无显著性差异），体脂下降也相似（-10.0±5.2 vs. -11.5±3.9 kg，无显著性差异）。然而，Trp64Arg等位基因携带者的内脏脂肪组织减少量比非携带者低43%（-46±27 vs. -81±51 cm²，P = 0.05）。此外，与该等位基因的非携带者相比，携带者的总胆固醇与高密度脂蛋白胆固醇比值改善较少（-0.18±0.54 vs. -0.72±0.56，P = 0.04）。虽然两组的葡萄糖代谢均有改善，但变体等位基因携带者和非携带者之间改善程度没有差异。总之，携带Trp64Argβ3 - 肾上腺素能受体基因变体的老年肥胖女性在长期热量限制下减少内脏脂肪组织的能力受损。尽管腹部脂肪组织减少存在这些基因差异，但两组之间葡萄糖代谢的改善相似。
