Background and aims: The fat mass and obesity associated gene (FTO) has been associated with obesity and dietary intake. The aims were: (i) To assess whether energy and macro-nutrient intakes were different across the FTOrs9939609 genotypes in adolescents, and (ii) to explore whether dietary fat intake modified the association of the rs9939609 polymorphism with adiposity. Methods and results: The FTOrs9939609 polymorphism was genotyped in 652 adolescents (53% females, 14.8 +/- 1.2 years, TT = 246, TA = 296, AA = 110). Energy and macronutrient intake were assessed by two non-consecutive 24 h-recalls. Weight, height, waist circumference and skinfold thicknesses were measured and body fat percent was calculated. Energy and macronutrient intake were similar across the FTOrs9939609 genotypes (P > 0.2). There were significant interactions between the FTO polymorphism and fat intake on adiposity estimates (P < 0.05). In adolescents whose fat intake was below 30% (N =203), the A allele of rs9939609 was not associated with adiposity indices. In contrast, in adolescents whose fat intake was between 30% and 35% of energy (N = 190), the rs9939609 polymorphismwas associated with a 1.9% higher body fat per risk allele (95% CI: 0.39, 3.33; P < 0.05), and in those whose fat intake was higher than 35% (N =259), it was associated with a 2.8% higher body fat per risk allele (95% CI: 1.27, 4.43; P < 0.001). Conclusions: These findings support the concept that the deleterious effect of the FTOrs9939609 polymorphism on adiposity is exacerbated in adolescents consuming high fat diets. In contrast, the consumption of low fat diets (< 30% of energy) may attenuate the genetic predisposition to obesity in risk allele carriers. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.