Impaired capacity to lose visceral adipose tissue during weight reduction in obese postmenopausal women with the Trp64Arg beta(3)-adrenoceptor gene variant

Controversy exists regarding the association between the Trp64Arg variant o f the beta(3)-adrenoceptor gene and visceral obesity. The cross-sectional n ature of most studies, the modest effect of the variant, and sex or ethnic differences between groups have contributed to discrepancies among investig ations. To overcome these confounding factors, we examined the effect of th e Trp64Arg variant on total and visceral adipose tissue loss, insulin sensi tivity, and cardiovascular disease risk factors in response to weight reduc tion in obese older women. A total of 24 women (age57 +/- 4 years), includi ng 1 Trp64Arg homozygote, 10 Trp64Arg heterozygotes, and 13 normal homozygo tes, were admitted to a weight reduction program of 13 +/- 3 months, with w eight and nutritional intake stabilization established before testing. Tota l and regional adiposity were measured with dual-energy X-ray absorptiometr y and computed tomography, insulin sensitivity was measured by the hyperins ulinemic-euglycemic clamp technique, and a blood lipid profile was obtained . No baseline differences were noted in adiposity measurements, glucose dis posal, and lipid profiles among carriers and noncarriers of the variant all ele. In response to weight loss, carriers and noncarriers of the Trp64Arg a llele 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, l oss of visceral adipose tissue was 43% lower in carriers of the Trp64Arg al lele compared with noncarriers (-46 +/- 27 vs. -81 +/- 51 cm(2), P = 0.05). Furthermore, there was less improvement in the total cholesterol-to-HDL ch olesterol ratio (-0.18 +/- 0.54 vs. -0.72 +/- 0.56, P = 0.04) in carriers c ompared with noncarriers of the allele. Although glucose disposal improved in both groups, there was no difference in the magnitude of improvement bet ween carriers and noncarriers of the variant allele. In conclusion, older o bese women carrying the Trp64Arg beta(3)-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 intra-abd ominal adipose tissue, improvement in glucose disposal was similar between groups.