Additive effect of the mutations in the β3-adrenoceptor gene and UCP3 gene promoter on body fat distribution and glycemic control after weight reduction in overweight subjects with CAD or metabolic syndrome

Objective: To analyze the effects of the mutations in the beta3-adrenoceptor (beta3-AR) gene and/or uncoupling protein3 (UCP3) gene promoter on body fat distribution and glycemic control after mild weight reduction in overweight-obese subjects with coronary artery disease (CAD) or metabolic syndrome. Design: Clinical intervention study of the -300 kcal/day mild weight reduction program for 12 weeks. Subjects: A total of 224 overweight-obese subjects with CAD or metabolic disorder, subdivided into the following four categories: (1) wild type (TT-CC, n=73); (2) only UCP3 promoter variant (TT-CT/TT, n=90); (3) only beta3-AR variant (TA/AA-CC, n=29); (4) both variants (TA/AA-CT/TT, n=32). Measurement: Body mass index (BMI), blood pressure, calorie intakes, body fat distribution, serum glucose, insulin, free fatty acids, C-peptide and lipids before and after weight reduction. Results: After 12 weeks, all subjects lost approximately 5% of their initial body weight. Despite similar weight reduction, the highest decreases in abdominal adipose tissue at both L1 and L4 levels were observed in the 'wild-type' group (P<0.001) and the second highest in 'only UPC3 promoter variant' group (P<0.001). On the other hand, both variant-carriers had the smallest reduction only in visceral fat area at the L4 level. All subjects except both variant-carriers showed significant reductions in the fasting levels of glucose and FFA. The response areas of glucose (P<0.01) and insulin (P<0.05) were reduced largest in the 'wild-type' group and second largest in the 'UCP3 promoter variant' group. Conclusion: All the four groups showed similar weight reduction after -300 kcal/d for 12 weeks. However, the beneficial effects on body fat distribution and glycemic control were greatest in the 'wild-type' group and smallest in 'both variants' group. In addition, these effects were less beneficial in carriers with beta3-AR gene variant than with UCP3 gene promoter variant.