Abstract

The fat mass and obesity–associated gene (FTO) has been shown to be associated with obesity and to influence appetite regulation. The aim was to examine whether dietary factors (macronutrient and fiber intakes) and leisure-time physical activity modify the association between genetic variation in FTO and body mass index (BMI; in kg/m2). A cross-sectional study examined 4839 subjects in the population-based Malmö Diet and Cancer study with dietary data (from a modified diet history method) and information on the genetic variant FTO (rs9939609). Direct anthropometric measures were made, and leisure-time physical activity was determined from the duration participants spent on 18 different physical activities. Significant interactions between energy-adjusted fat intake and FTO genotype (P = 0.04) and between carbohydrate intake and FTO genotype (P = 0.001) on BMI were observed. The observed increase in BMI across FTO genotypes was restricted to those who reported a high-fat diet, with a mean BMI of 25.3 (95% CI: 24.9, 25.6) among TT carriers and of 26.3 (95% CI: 25.8, 26.8) among AA carriers (P = 0.0001). The FTO variant was not associated with a higher BMI among subjects with lower fat intakes (BMI = 25.7 and 25.9 in TT carriers and AA carriers, respectively; P = 0.42). Among individuals with a low-carbohydrate intake, we observed a mean BMI of 25.4 for TT carriers and of 26.8 for AA carriers. The increase in BMI across genotypes was mainly restricted to individuals who reported low leisure-time physical activity (P for trend = 0.004, P for interaction = 0.05). Our results indicate that high-fat diets and low physical activity levels may accentuate the susceptibility to obesity by the FTO variant.