Acetyl-CoA acyltransferase 2 palmitoylation drives liver fibrosis by inducing hepatic stellate cell ferroptosis.

ABSTRACT: Hepatic fibrosis is a major driver of mortality in metabolic dysfunction-associated steatotic liver disease (MASLD)-previously known as non-alcoholic fatty liver disease (NAFLD). While hepatic stellate cell (HSC) activation and myofibroblast accumulation are central to fibrogenesis, the regulatory mechanisms remain incompletely understood. Acetyl-CoA acyltransferase 2 (ACAA2), a pivotal enzyme in fatty acid oxidation, has been implicated in lipid metabolism but has not been investigated as a therapeutic target in MASLD. Here, we show that ACAA2 upregulation in HSCs exacerbates hepatic fibrosis by promoting ferroptosis-associated transcriptional programs, whereas ACAA2 inhibition attenuates both ferroptosis and fibrogenesis in preclinical models. Mechanistically, ACAA2 palmitoylation govern

SUBMITTER: Han J 

PROVIDER: S-EPMC12859212 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature