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Purpose  Poor physical fitness and obesity are risk factors for all cause morbidity and mortality. We aimed to clarify whether common genetic variants of key energy intake determinants in leptin ( LEP ), leptin receptor ( LEPR ), and fat mass and obesity-associated ( FTO ) are associated with aerobic and neuromuscular performance, and whether aerobic fitness can alter the effect of these genotypes on body composition.    Methods  846 healthy Finnish males of Caucasian origin were genotyped for  FTO  (rs8050136),  LEP  (rs7799039) and  LEPR  (rs8179183 and rs1137101) single nucleotide polymorphisms (SNPs), and studied for associations with maximal oxygen consumption, body fat percent, serum leptin levels, waist circumference and maximal force of leg extensor muscles.    Results  Genotype AA of the  FTO  SNP rs8050136 associated with higher BMI and greater waist circumference compared to the genotype CC. In general linear model, no significant interaction for  FTO  genotype-relative VO 2 max (mL·kg −1 ·min −1 ) or  FTO  genotype-absolute VO 2 max (L·min −1 ) on BMI or waist circumference was found. Main effects of aerobic performance on body composition traits were significant (p<0.001). Logistic regression modelling found no significant interaction between aerobic fitness and  FTO  genotype.  LEP  SNP rs7799039,  LEPR  SNPs rs8179183 and rs1137101 did not associate with any of the measured variables, and no significant interactions of  LEP  or  LEPR  genotype with aerobic fitness were observed. In addition, none of the studied SNPs associated with aerobic or neuromuscular performance.    Conclusions  Aerobic fitness may not modify the effect of  FTO  variation on body composition traits. However, relative aerobic capacity associates with lower BMI and waist circumference regardless of the  FTO  genotype.  FTO ,  LEP  and  LEPR  genotypes unlikely associate with physical performance.

Aerobic Fitness Does Not Modify the Effect of FTO Variation on Body Composition Traits