SIRT1 acts as a cellular sensor to detect energy availability and modulates fat and glucose metabolism. This study assessed the effects of self-reported calorie restriction (CR) and exercise on correlations between SIRT1 polymorphisms and body mass index (BMI) and long-term weight change. This cross-sectional study enrolled 4023 subjects aged 35–69 years (1847 men and 2176 women) selected from participants in the Japan Multi-Institutional Collaborative Cohort Study. This study was based on a self-administered questionnaire. No significant correlations between SIRT1 polymorphisms and BMI or long-term weight change were found in either the CR or the active groups. In the no-CR group, women with the rs1467568 G allele had a higher BMI than women without (p = 0.02). Moreover, women with the rs7895833 A or rs1467568 G allele gained more weight from the age of 20 years than women without these alleles (p = 0.03 for rs7895833 and p = 0.003 for rs1467568). In addition, the odds ratios (95% confidence intervals) of these alleles for overweight (BMI > 27.5 kg/m2) were significantly high in the no-CR women group (1.78 (1.06–2.99) for rs7895833 and 1.88 (1.13–3.15) for rs1467568) but not in the CR group. The results of this study suggest that CR might override the genetic contributions of the SIRT1 rs7895833 A and rs1467568 G alleles to BMI and long-term weight change.
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