Obesity, characterized by excessive fat accumulation, disrupts metabolism, leading to insulin resistance, hyperglycemia, and dyslipidemia. Circadian rhythm genes such as BMAL1 and CRY1 regulate energy balance, lipid metabolism, and glucose homeostasis, with enzymes, for example, DGAT1 and DGAT2, playing critical roles in triglyceride synthesis. Melatonin, a circadian regulator, influences metabolic processes, including glucose and insulin regulation. This study examined melatonin's therapeutic effects in obese Wistar rats. A total of 48 male rats were fed either a standard diet (C group) or a high-fat diet for 11 weeks to induce obesity. Once the obese group was established, the latter animals were subdivided into two experimental groups, namely, OB (obesity-induced) and OB-M (obesity-induced + melatonin), each under two circadian shifts (9 h and 21 h). During the subsequent 6 weeks, all animals received standard diets plus/minus melatonin supplementation (25 µg/mL in drinking water). The 9 h and 21 h time points were selected to evaluate the effects of circadian rhythm alignment or disruption on metabolic outcomes and melatonin efficacy. Body weight, food intake, and water consumption were recorded every third day. Melatonin supplementation significantly reduced body weight in OB-M group, with no effect observed in the control animals. It also improved glucose, cholesterol, and triglyceride levels compared to diet change alone. Leptin and IL-1β levels decreased with melatonin, suggesting anti-inflammatory and metabolic regulatory effects. Additionally, melatonin influenced circadian gene expression, including BMAL1 and CRY1, and showed correlations with metabolic and inflammatory markers. These findings indicate that melatonin supplementation, when combined with dietary modifications, improves metabolic outcomes and contributes to the restoration of circadian and inflammatory balance in obesity. However, further research is required to elucidate the underlying mechanisms.
