Ameliorating effects of melatonin on high-fat diet induced non-alcoholic fatty liver diseases and their associated pathologies: A comprehensive review

Non-alcoholic fatty liver disease (NAFLD) is caused by hepatic fat accumulation with a high prevalence globally, especially in Western countries in which individuals have excessive fat consumption. Prolonged intake of high dietary fat causes various diseases due to the imbalance of energy metabolism, which leads to obesity and other pathological conditions. Currently, the exact pathogenesis of NAFLD is still obscure. In this review, the potential etiologies for NAFLD will be discussed, including adipose tissue dysfunction, intrahepatic de novo lipogenesis, hepatic fat accumulation, insulin resistance, hepatic inflammation, inflammasome activation, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress. Melatonin is a potent antioxidant and anti-inflammatory molecule. It is also a regulator of lipid and glucose metabolism which is indicated by melatonin’s effects on weight loss, reduction of liver weight, blood levels of lipids, glucose and insulin, activities of hepatic enzymes, steatohepatitis, and fibrosis. Melatonin considerably reduces mitochondrial dysfunction and proinflammatory cytokines. Moreover, it downregulates NLRP3 and its associated downstream effectors of caspase-1, IL-1β, and IL-18 proteins. This review will update the molecular mechanisms behind high-fat diet induced hepatic dysfunction and the protective role of melatonin in NAFLD.