Arachidonic acid metabolism in metabolic dysfunction-associated steatotic liver disease and liver fibrosis

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder globally, affecting 30% of the population and causing a significant healthcare burden due to its increasing incidence and limited therapeutic options. Arachidonic acid (AA) is a key bioactive lipid precursor that generates eicosanoids, such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acids, via 3 distinct enzymatic pathways: cyclooxygenase, lipoxygenase, and cytochrome P450. Emerging evidence indicates that AA-derived metabolites and pathway factors contribute to the progression and severity of MASLD and liver fibrosis. This review systematically summarizes the pathophysiological roles of AA metabolism in MASLD and liver fibrosis, focusing on mechanisms involving lipid accumulation, liver inflammation, fibrogenesis, and related cellular processes. In addition, we discuss potential therapeutic targets within the AA metabolic pathway in MASLD and liver fibrosis, highlighting emerging clinical advances targeting AA metabolites and pathway factors to improve these pathological conditions.