HIF-1α Regulates the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease

With the improvement in living standards, metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease worldwide, garnering increasing concern due to its significant health risks. MASLD encompasses a spectrum of pathological processes ranging from simple steatosis to nonalcoholic steatohepatitis, liver fibrosis, cirrhosis, and even hepatocellular carcinoma, and it has become a leading cause of liver-related mortality. Due to the lack of specific therapeutic targets, current diagnostic, treatment, and management strategies for MASLD remain inadequate.

This review aims to explore the pathophysiological manifestations of MASLD, the mechanisms through which hypoxia-inducible factor-1α (HIF-1α) contributes to disease progression, and the potential therapeutic approaches targeting HIF-1α, offering feasible strategies for treating advanced MASLD.

Studies suggest that hepatocytes in MASLD are often in a hypoxic state, which activates HIF-1α, playing a crucial role in disease progression. During hypoxia, the expression of HIF-1α increases throughout the different stages of MASLD, interacting with various genes and pathways, influencing lipid metabolism, steatosis, and fibrosis progression.