Nutritional c-Fos Induction Rewires Hepatic Metabolism and Can Promote Obesity-Associated Hepatocellular Carcinoma.

ABSTRACT: The transcription factor c-Fos plays a key role in liver metabolism, stress responses, and carcinogenesis. Here, the role of hepatic c-Fos in the pathophysiology of metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma (HCC) is investigated. In chow-fed mice, hepatic c-Fos is induced by insulin after feeding and suppressed by glucagon during fasting. Adenovirus-mediated hepatic c-Fos ectopic expression is sufficient to induce insulin resistance in chow-fed mice. In models of diet-induced obesity and inducible hepatocyte-specific Fos-expressing mice, elevated c-Fos expression is associated with transcriptomic changes in PPAR signaling and fatty acid metabolism pathways. Mechanistically, ectopic c-Fos expression enhances glycolysis and activates stress-related

SUBMITTER: Li A 

PROVIDER: S-EPMC12713005 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature