Uncoupling protein 1 gene −3826 A/G polymorphism is associated with weight loss on a short-term, controlled-energy diet in young women

Uncoupling protein 1 (UCP1) plays an important role in thermogenesis in brown adipose tissue. Previously, we reported an association between −3826 A/G single-nucleotide polymorphism (SNP) in the promoter of UCP1 gene and lower thermogenesis in young women, suggesting this SNP has an adverse effect on the regulation of energy balance. Based on the hypothesis that this SNP (G allele) may have resistance against diet-induced weight loss, we examined its effects on anthropometric and metabolic responses to short-term, controlled-energy diet in young women. Seventeen lean women (20.9 ± 0.2 years; body mass index, 22.1 ± 0.5 kg/m2) were fed a controlled-energy diet (5.0 MJ/d, 62% carbohydrate, 19% protein, and 19% fat) administered by dietitians for 2 weeks. Clinical measurements were determined at baseline and after the dietary intervention. The subjects' physical activity was obtained using pedometers and self-reporting. The thermoregulatory sympathetic nervous system was evaluated using heart rate variability power spectral analysis. Upon the completion of the intervention, subjects were genotyped using an allele-specific DNA primer assay and results compared with their clinical measurements focusing on with or without the G allele. After dietary intervention, G allele subjects (A/G + G/G, n = 10) showed significantly smaller changes in body weight, body mass index, and waist circumference compared with A/A genotype subjects (n = 7). Similar changes were observed in parameters regarding glucose or lipid metabolism in both groups. These results suggest that the UCP1 gene −3826 G allele may result in smaller weight loss after a short-term, controlled-energy diet in young, lean women.