Melatonin and its agonist ameliorate anthropometric and biochemical variables in high-fat plus high-fructose fed rats

Background: High-fat and fructose-rich diets are known to trigger obesity, lipid abnormalities, and organ damage in rats, closely resembling the features of human metabolic syndrome. Melatonin and its synthetic agonists have been suggested as possible protective agents, but their effects in this context remain unclear. Aims: This study set out to assess the protective role of melatonin and its agonist (agomelatine) against the negative impacts of a high fat and high fructose diet (HFHFD) diet in rats, focusing on body measurements, biochemical markers, adipokines (omentin and chemerin), oxidative stress, and tissue health. Materials and Methods: Thirty-two male Wistar rats were randomly assigned to four groups (n=8 each): control, HFHFD, HFHFD + melatonin, and HFHFD + agomelatine. The treatments continued for 10 weeks. Anthropometric parameters were monitored. Serum biochemical parameters (lipid profile, glucose, MDA, liver and kidney function tests) and adipokine levels were measured using ELISA and standard assays. Histological examination of liver and adipose tissues was performed with hematoxylin–eosin staining. Data were analyzed using ANOVA followed by post hoc testing. Results: Rats fed HFHFD showed increases in cholesterol, triglycerides, LDL, ALP, fat mass, adiposity index, and marked liver and adipose damage. Melatonin and agomelatine reduced weight gain, fat accumulation, and adiposity index, confirming anti-obesity effects. Melatonin further improved cholesterol, LDL, ALP, and preserved tissue by reducing fat cell enlargement, steatosis, and inflammation. Both agents affected adipokines, with melatonin tending to raise omentin (not significant). Agomelatine lowered weight more strongly but offered less liver protection, with persistent steatosis and necrosis. Conclusions: Melatonin and its agonist countered obesity-related changes in HFHFD-fed rats, but melatonin provided broader benefits by improving lipid profile, lowering ALP, and preserving tissue integrity. Agomelatine reduced body weight more effectively yet offered less liver protection. Overall, melatonin appears the more promising candidate against diet-induced metabolic and structural damage.