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Hepatocyte FoxO1 depletion exacerbates hepatic inflammation in MASH

ABSTRACT: The transcription factor Forkhead box protein O1 (FoxO1) is a well-established regulator of glucose and lipid metabolism, yet its role in metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis remains debated. This study investigates hepatocyte-specific FoxO1 mechanisms driving hepatic inflammation in MASH. Using hepatocyte-specific FoxO1-knockout (KO) mice fed a methionine-choline-deficient diet and LPS-treated FoxO1-KO cells, we demonstrate FoxO1 depletion exacerbates hepatic inflammation, ballooning degeneration, and upregulates TNF-alpha, CXCL8, and CXCL2 in vivo and in vitro. Transcriptomics linked FoxO1 deficiency to enriched pro-inflammatory pathways and suppressed cysteine/methionine metabolism.

ORGANISM(S): Homo sapiens

PROVIDER: GSE293003 | GEO | 2025/07/30

REPOSITORIES: GEO

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Project description:Hepatocyte FoxO1 depletion exacerbates hepatic inflammation in MASH

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