Topic: Hepatic Lipid Metabolism and Liver Injury: From Mechanism to Therapeutics

Hepatic lipid metabolism is a double-edged sword, which is essential for systemic energy homeostasis, yet a central driver of liver injury when dysregulated. The spectrum of metabolic liver disease covers from metabolic dysfunction-associated steatotic liver disease to alcohol-associated injury and toxicant-induced hepatotoxicity, which converges on shared pathological nodes including de novo lipogenesis, excessive fatty acid oxidation, lipotoxicity, and the activation of fibrogenic programs within hepatic stellate cells. Mechanistic advances have illuminated how transcription factors such as SREBP-1c and PPARα, nutrient sensors like AMPK and SIRT1, and autophagic flux through lipophagy dictate whether lipids are safely stored or become instruments of cellular damage. Emerging evidence further implicates inter-organ crosstalk, epigenetic reprogramming, and cell-specific metabolic remodeling in shaping liver injury outcomes. This special issue brings together original research and reviews that interrogate these mechanisms at the molecular, cellular, and organismal levels, while translating those insights toward therapeutic strategies that aim to restore hepatic lipid equilibrium and halt the progression from steatosis to fibrosis and failure. We welcome contributions that bridge mechanistic depth with therapeutic relevance, ultimately advancing the goal of precision management for lipid-driven liver disease.