HIF-2α-driven Lipogenesis and Inflammation in Metabolic Dysfunction-associated Steatotic Liver Disease: Role of ATF4 Signaling.

ABSTRACT:

Background & aims

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an imbalance of lipid metabolism and chronic inflammation. Emerging evidence suggests a role for hypoxia-inducible factor 2α (HIF-2α) in MASLD progression. However, the mechanistic linkage between HIF-2α and steatohepatitis progression remains largely elusive.

Methods

Here, hepatocyte-specific HIF-2α knockout mice were used to investigate the pathophysiological role of HIF-2α in MASLD. Multiple gain- and loss-of-function experiments in primary hepatocytes and established human hepatocyte cell lines were performed to elucidate the molecular mechanisms by which HIF-2α contributes to MASLD progression.

Results

Compared with their wild-type littermates, hepatocyte-specif

SUBMITTER: Yang Z 

PROVIDER: S-EPMC12681847 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature