HIF-1α regulates the progression of metabolic dysfunction-associated steatotic liver disease.

Abstract

Background: 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 non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC), 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.

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

Key message: Studies suggest that hepatocytes in MASLD are often in a hypoxic state, which activates hypoxia-inducible factor-1α (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.