Systematic review of melatonin metabolism and circadian cycle regulation in the treatment of obesity and liver diseases

Abstract

Introduction: In the context of obesity and liver disease, sleep disorders are associated with several metabolic disorders, including insulin resistance, obesity, hypertension, fatty liver disease, and cardiometabolic complications. In this regard, melatonin (N-[2-(5-methoxy-1H-indol-3-yl)ethyl] acetamide) stands out. It is a neurohormone secreted by the pineal gland and plays a fundamental role in maintaining the circadian rhythm. Objective: To present the main considerations regarding the importance of melatonin and circadian regulation, as well as the effect of melatonin supplementation on obesity and liver disease. Methods: The systematic review guidelines of the PRISMA Platform were followed. The search was conducted from May to June 2025 across the Scopus, Embase, PubMed, and ScienceDirect, Scielo, and Google Scholar databases. Study quality was based on the GRADE instrument, and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 182 articles were found. A total of 58 articles were evaluated, and 51 were included in this systematic review. Using the Cochrane risk of bias tool, the overall assessment resulted in 15 studies with a high risk of bias and 21 studies that did not meet the GRADE criteria. Most studies presented homogeneous results, with X²=95.8%>50%. It was concluded that metabolic and liver diseases affect thousands of individuals worldwide, worsening quality of life and mainly compromising the productive period. Studies involving drug and molecular therapies are proposed to control the progression of these diseases. A molecular analysis involving epigenetic, biochemical, and inflammatory aspects related to melatonin supplementation is needed to clarify the effect of melatonin supplementation on obesity and liver diseases, including NAFLD and HCC. The elucidation of the antioxidant and antiinflammatory effect of melatonin and its use as a synergistic agent in weight loss, as well as in liver diseases, in personalized treatment, were highlighted.