Diabetes, Vol 49, Issue 10 1709-1713, Copyright © 2000 by American Diabetes Association
Impaired capacity to lose visceral adipose tissue during weight reduction in obese postmenopausal women with the Trp64Arg beta3-adrenoceptor gene variant
A Tchernof, RD Starling, A Turner, AR Shuldiner, JD Walston, K Silver and ET Poehlman
Department of Medicine, College of Medicine, University of Vermont, Burlington 05405, USA.
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.