Associations among melanocortin-4 receptor rs17782313 gene polymorphisms, 12-week aerobic exercise combined with low-fat diet and degree of reduction in blood lipids in adults with obesity.

Purpose: This study investigates the relationships between melanocortin-4 receptor (MC4R) rs17782313 gene polymorphisms, low-fat diet, aerobic exercise, and the reduction in blood lipid levels in individuals with obesity.

Methods: A total of 240 adults living with obesity were enrolled to take part in a 12-week program that combined exercises with dietary interventions. Measurements taken included body weight, body mass index (BMI), plasma lipids, fasting insulin (FIN), and insulin resistance (Homeostasis Model Assessment, HOMA-IR). All participants underwent exercise intervention and genotyping.

Results: Our findings revealed significant interactions between genotype, sex, and diet in modulating lipid metabolism. Specifically, after the exercise intervention, the mean reduction in BMI in was: CC+CT with low-fat diet: -2.56 ± 1.98 kg/m; CC+CT with regular diet: -1.00 ± 0.99 kg/m; TT with low-fat diet: -1.89 ± 1.31 kg/m; TT with regular diet: -0.85 ± 0.68 kg/m. Males with CC+CT genotypes exhibited significant improvements in low-density lipoprotein (LDL-C) (P<0.05) and insulin resistance (P<0.05) on a low-fat diet, while changes in high-density lipoprotein (HDL-C) were not significant ( > 0.05). Triglyceride (TG) reduction was most pronounced in males with CC+CT genotypes on a low-fat diet and regular diet(effect sizes:-0.75,  = 0.018), though genotype-diet interactions for TG reached statistical significance ( = 0.02). These males also showed a significant decrease in LDL-C between a low-fat diet with CC+CT genotypes and regular diet with TT genotypes (effect sizes -0.46,  = 0.008), though genotype-diet interactions for LDL-C on those two groups reached statistical significance ( = 0.01). However, this decrease was not significantly different from that in females with the CC+CT genotypes. Trends in FIN changes were similar to those in LDL-C between low-fat diet with CC+CT genotypes and regular diet with TT genotypes groups (effect sizes -12.88, P<0.001). Additionally, HOMA-IR scores reduction was most pronounced in males with CC+CT genotypes on a low-fat diet and regular diet (effect sizes-2.90, P<0.001).

Conclusion: The CC+CT genotype group, particularly males on a low-fat diet, showed robust improvements in TG, LDL-C, and insulin resistance markers. However, HDL-C responses were inconsistent across subgroups. Notably, males with the CC+CT allele exhibited the most pronounced benefits in LDL-C reduction and HOMA-IR improvement with a low-fat diet.