Synergistic impact of melatonin and orlistat had more desirable effects on glucose metabolism, inflammation, and oxidative stress in obese rats

Obesity, a metabolic disorder, has emerged as a significant public health concern, ranking as the fifth leading cause of death worldwide. Despite several attempts to combat this condition, it has been unsuccessful and the WHO predicted that it might lead to 30% of deaths globally by the year 2030. This has led to the quest of finding a novel therapeutic agent (Nikniaz et al., 2023). Studies have demonstrated a direct correlation between increased body weight, altered reproductive parameters, hormonal imbalance, and elevated mortality rates. The treatment of obesity has recommended Orlistat, a gastrointestinal lipase inhibitor. However, the gastrointestinal side effects have discouraged most patients from its continuous usage (Bansal et al., 2022). Researchers have reported that melatonin, a widely used alternative medicine, effectively reduces body weight with minimal side effects. Therefore, the present study investigated the effects of co-administration of melatonin and orlistat in the obesity model of male Wistar rats weighing between 120 – 140 g. We hypothesized that the combined administration of melatonin and orlistat does not act as an anti-obesogenic therapy on the obese rat model. We divided thirty (30) rats, each consisting of five (5) animals, into the following groups: control (untreated), high fat diet (HFD), high fat diet recovery (hfd), hfd + melatonin (4 mg/kg), hfd + orlistat (30 mg/kg), and HFD + melatonin (4 mg/kg) + orlistat (30 mg/kg). Adeyemi et al., 2020 induced obesity in the rats by exposing them to a high-fat diet for 16 weeks. The rats underwent a 21-day treatment, following which they received an intramuscular injection of 50 mg/kg of ketamine to induce anesthesia. We administered melatonin and orlistat at 4 and 30 mg/kg b.w., p.o., respectively. We analyzed the data using analysis of variance and the LSD post hoc test, both at the 0.05 significance level. The results revealed that the induced obesity led to significant increases in plasma glucose, plasma insulin, and HOMA-IR. Compared to the obese control, treatments with single administration of melatonin or orlistat resulted in significant elevations in total antioxidant capacity (TAC), catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx); however, there was a significant decrease in interleukin 6 (IL-6), C-reactive protein (CRP), and tumor necrotic factor (TNF-a). Compared to a single administration of melatonin or orlistat, the combined administration of melatonin and orlistat yielded more favorable results on all indices. Hence, it was concluded that the combined administration of melatonin and orlistat could be beneficial in the management of obesity. The authors would like to acknowledge that this is a self-funding project. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.