A Comprehensive Review of Pathophysiological Link Between Non-alcoholic Fatty Liver Disease, Insulin Resistance, and Metabolic Syndrome.

Non-alcoholic fatty liver disease (NAFLD) is a chronic condition characterized by hepatic steatosis in the absence of significant alcohol consumption and is increasingly recognized as the hepatic manifestation of metabolic syndrome (MetS). This review aims to explore the molecular mechanisms underlying the interaction between NAFLD, insulin resistance (IR), and MetS, with a focus on identifying therapeutic targets. A comprehensive review of existing literature on NAFLD, IR, and MetS was conducted. The review indicates that IR contributes to hepatic lipid accumulation through increased lipolysis, elevated free fatty acid flux, and impaired fatty acid oxidation, while MetS exacerbates the condition by promoting visceral adiposity, chronic inflammation, and impaired lipid metabolism. Additionally, dysbiosis and increased intestinal permeability in the gut-liver axis worsen IR, leading to a vicious cycle of metabolic dysfunction. In conclusion, addressing these interconnected pathways could enhance therapeutic strategies and reduce the burden of NAFLD-related complications.