The association of <i>SLC16A1</i> (<i>MCT1</i>) gene polymorphism with body composition changes during weight loss interventions: A randomized trial with sex-dependent analysis

Monocarboxylates, transported by monocarboxylate transporters (MCTs), have been proposed to influence energy homeostasis and exhibit altered metabolism during exercise. This study investigated the association between the Asp490Glu (T1470A) (rs1049434) polymorphism of the <i>SLC16A1</i> (<i>MCT1</i>) gene and changes in body composition in males and females with overweight or obesity. The 173 participants (56.6% females) completed a 6-month randomized controlled trial, being assigned to the Supervised Exercise group (strength, endurance, or strength plus endurance training) or the Physical Activity (PA) Recommendations group. Participants were genotypically categorized as Asp/Asp (TT), Asp/Glu (TA), or Glu/Glu (AA). ANCOVA analysis showed main effects for genotype and interaction genotype × group (<i>p</i> < 0.05) for several variables, especially in females. Asp/Asp (TT) females showed greater reductions in total fat mass (-29.30 ± 8.75% change), percentage of body fat (-17.50 ± 8.06% change), and body weight (-13.90 ± 2.62% change) compared with Glu/Glu (AA) (<i>p</i> ≤ 0.020; <i>d</i> ≥ 0.18) and Asp/Glu (TA) (<i>p</i> ≤ 0.050; <i>d</i> ≥ 0.16) females, but only within the PA Recommendations group. Data indicated higher decreases in lean body mass of the Asp/Asp (TT) compared to Glu/Glu (AA) in females (<i>p</i> = 0.067, η² _p = 0.067) and to Asp/Glu (TA) in males (<i>p</i> = 0.026; η² _p = 0.101). Our investigation suggests an association of the single-nucleotide polymorphism with body composition changes especially in females following exercise recommendations, highlighting the importance of supervised training to offset genetic predisposition for different weight loss. Differences in males only appeared for lean body mass, suggesting sex differences for this genetic association. The study underscores the potential influence of MCT1 functionality on human adaptations to weight loss interventions. ClinicalTrials.gov information: registry name, Nutrition and Physical Activity for Obesity (PRONAF); registration number, NCT01116856.