The relationship between body fat distribution, CLOCK, BMAL1, MC4R genetic polymorphisms, melatonin levels, and metabolic parameters in obese patients

Melatonin levels are found to be low in obese patients, but the exact mechanism through which it plays a role in the pathogenesis of obesity has not yet been clarified. In our study, we aimed to determine the mechanism of melatonin in the pathogenesis of obesity by investigating body fat distribution, GLP-1, ghrelin levels, CLOCK, BMAL1, MC4R genetic polymorphisms, and their relationships with each other. A total of 161 participants, including 81 obese individuals and 80 controls, aged 18 to 65 years, were included in the study. After an overnight fast, venous blood samples were collected from participants in the morning for fasting blood glucose, insulin, low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, ghrelin, GLP-1, melatonin levels, and genetic analysis. Serum ghrelin, GLP-1, and melatonin levels were assessed using the ELISA method. Body mass index was calculated, and ultrasound analysis was performed to determine body fat distribution. DNA isolation from blood samples and RT-PCR were used for the analysis of genetic polymorphisms. Additionally, a morning/evening questionnaire was administered to assess the participants' chronotype. As a result, the obese group had significantly higher subcutaneous, preperitoneal, and visceral fat distribution compared to the control group (p<0.05). Melatonin and GLP-1 levels were significantly lower (p<0.05) in the obese group compared to the control group, while ghrelin levels were significantly higher (p<0.05). Furthermore, we found that the TA variant of the MC4R RS 17782313 polymorphism was more frequent in the obese group compared to the control group. No significant differences were found between the groups for CLOCK T/C RS1801260, MC4R RS12970134, and BMAL1 RS6486121 genetic polymorphisms. We could not find a significant relationship between melatonin levels, genetic polymorphisms, GLP-1, ghrelin, body fat distribution, and questionnaire results. These findings suggest that the MC4R RS 17782313 polymorphism and melatonin are associated with obesity, but their mechanisms are not interrelated." Keywords: obesity, melatonin, GLP-1, ghrelin, body fat distribution, genetic polymorphisms