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The human locus FNDC5 rs16835198 contributes positively to anthropometric phenotypes in children and adolescents. However, the role of specific components of physical fitness in this relationship is not known. The present study aimed to verify the moderator role of cardiorespiratory fitness (CRF) and muscular strength in the relationship between rs16835198 polymorphism FNDC5 and adiposity in children and adolescents. This cross-sectional study was carried out by genotyping the rs16835198 FNDC5 polymorphism in 1701 children and adolescents (mean age 11.73 ± 2.75 years). Obesity was assessed using waist circumference and body mass index (BMI) z-scores. To evaluate CRF and muscular strength, the 6 min run/walk test and lower limb strength (LLS) were used. Linear regression models were applied, and all analyses were adjusted for age, sex, skin color, living area, and school type. A significant interaction term for CRF ( p = 0.038) and LLS ( p = 0.040) × rs16835198 FNDC5 with WC was identified. Regarding BMI, a significant interaction term for CRF ( p = 0.007) and LLS ( p = 0.044) × rs16835198 FNDC5 was observed. Moreover, medium and high CRF and LLS levels protected against higher WC and BMI. In conclusion, adiposity levels of children and adolescents with a genetic predisposition to obesity might be modified by improving CRF and muscular strength.

Cardiorespiratory Fitness and Muscular Strength Moderates the Relationship between FNDC5 Polymorphism and Adiposity in Children and Adolescents