Does the MC4R RS17782313 gene polymorphism affect the rate of exercise-induced fat oxidation?

Aim: The aim of this study was to investigate the effect of the MC4R rs17782313 gene polymorphism on exercise-induced fat oxidation in individuals who do not engage in regular physical activity. Material and Method: A total of 48 sedentary male volunteers aged between 20 and 30 years, with no health restrictions for exercise, were included in the study. Participants underwent a graded exercise test during which VO₂, RQ, and substrate utilization were measured. Fat and carbohydrate oxidation rates were calculated based on data obtained from respiratory gas analysis. Participants were grouped according to their genotype (risk C-allele carriers and TT homozygotes), and group means for VO₂, RQ, FAT, CHO, and BMI were compared using statistical tests. Data were analyzed using IBM SPSS 24 software, and differences between groups were evaluated with the Wilcoxon test. Results: The study found that body mass index (BMI) and body weight values differed significantly among the genotypes (p<0.05). Furthermore, under the dominant model, the CC+TC genotype group showed a significantly higher BMI compared to the TT genotype group (t=3.180; p<0.05). In terms of aerobic capacity, VO₂ mean values differed by genotype. Specifically, in the dominant model, the 3-minute VO₂ average of the TT genotype group (mean = 941.860) was significantly lower than that of the CC+TC group (mean = 1047.057) (t=2.284; p<0.05). Similarly, the 9-minute VO₂ average of the CC+TC group (mean = 1709.733) was significantly higher than that of the TT group (mean = 1536.901) (t=2.284; p<0.05). However, no significant differences were observed between genotypes in respiratory quotient (RQ), fat oxidation (FAT), or carbohydrate oxidation (CHO) values during moderate-intensity exercise (p>0.05). Conclusions: These findings suggest that the MC4R rs17782313 polymorphism may be associated with higher body fat mass, but it does not appear to directly affect acute fat oxidation processes during exercise. Therefore, the contribution of this genetic variant to obesity risk is more likely mediated through behavioral and neuroendocrine mechanisms influencing energy intake, rather than through metabolic limitations in fat utilization.