Difficulty in losing weight by behavioral intervention for women with Trp64Arg polymorphism of the β3-adrenergic receptor gene

Abstract

OBJECTIVE: Trp64Arg mutation in the b 3 -adrenergic receptor (b 3 AR) gene is relatively common in Japanese people. However, it has not been clear whether persons with Trp64Arg mutation in the b 3 AR gene tend to have obesity and difficulty in losing weight even with a restricted diet and exercise. We investigated the response of body weight and metabolic factors to behavioral intervention in Japanese women with Trp64Arg mutation in the b 3 AR gene. DESIGN: A 3-month behavioral intervention study using a combination of diet and exercise programs. SUBJECTS: A total of 76 perimenopausal women with no clinical symptoms (age: 54.777.7 y, body mass index (BMI): 21.0-33.0 kg/m 2 ). MEASUREMENTS: Anthropometric measurements (weight, height, body fat, waist circumference, hip circumference, skin fold, resting energy expenditure and blood pressure) and metabolic measurements (serum levels of cholesterol, triglyceride, phospholipid, nonesterified fatty acid, glucose, insulin and leptin) and determination of the b 3 AR genotype by polymerase chain reaction followed by BstNI digestion. RESULTS: At the baseline of BMI, body weight, body fat, waist circumference, hip circumference, the arm skin fold, resting energy expenditure, or blood lipid and glucose profiles, there was no significant difference in participants with/without mutation of the b 3 AR gene. The intervention yielded a body weight reduction in 69 and 48%, and induced a significant difference in weight loss (À0.74 and À0.01 kg) for women with wild-type and Trp64Arg mutation, respectively. Significant differences of anthropometric parameters were found in body weight, BMI, waist and hip circumferences and blood pressure of wild type by the intervention. However, women with Trp64Arg mutation did not show significant changes in these anthropometric parameters, except for hip circumference. A significant difference was found in high-density lipoprotein cholesterol (HDL-C) and in the low-density lipoprotein cholesterol/HDL-C ratio in both genotypes. CONCLUSION: The results of the present study suggest that the Trp64Arg mutation of the b 3 AR gene is associated with difficulty in losing weight through behavioral intervention, although it is not related to obesity-related phenotypes and resting energy expenditure before the intervention.

Effect of β3-adrenergic receptor gene polymorphism on body weight change in middle-aged, overweight women

“…In the present study, the frequency of the 64Arg allele was 0.25, and this allele frequency was similar to those (0.19 to 0.23) that were reported among Japanese women in other studies (27)(28)(29). In the present study, subjects with the 64Arg allele had significantly smaller decreases in BW after the 12-week BW reduction program than those without the 64Arg allele as in other Japanese studies (27)(28)(29).…”

“…In the present study, subjects with the 64Arg allele had significantly smaller decreases in BW after the 12-week BW reduction program than those without the 64Arg allele as in other Japanese studies (27)(28)(29). However, a significant difference in change of energy intake was observed between subjects with and without the 64Arg allele.…”

“…Baseline BW and BMI were not different between the subjects with and without the 64Arg allele in this study as in other Japanese studies (27)(28)(29). Two meta-analyses of the correlation of β 3 -AR gene polymorphism with BMI led to different conclusions.…”

“…Studies conducted in Finland (22), France (23) and Germany (25) could not elucidate the effect of β 3 -AR gene polymorphism on the response to the BW reduction programs. In contrast, studies conducted in Japan (27)(28)(29) showed that subjects with the 64Arg allele have smaller decreases in BW after 12-week BW reduction programs than those without the 64Arg allele, although the baseline BMI showed no difference between those with and without the 64Arg allele.…”

“…Previous intervention studies showed that there is no significant difference in the magnitude of BW loss between those with and without the 64Arg allele (19,(22)(23)(24)(25)(26). However, other studies showed that subjects with the 64Arg allele had difficulty in losing BW (27)(28)(29), or had difficulty in losing visceral fat (24) or abdominal adipose tissue (30) during BW reduction programs. These discrepancies among investigations might be explained by lifestyle factors including energy intake and expenditure.…”