Metabolic nuclear receptors coordinate energy metabolism to regulate Sox9⁺ hepatocyte fate.

ABSTRACT: Recent research has indicated the adult liver Sox9⁺ cells located in the portal triads contribute to the physiological maintenance of liver mass and injury repair. However, the physiology and pathology regulation mechanisms of adult liver Sox9⁺ cells remain unknown. Here, PPARα and FXR bound to the shared site in Sox9 promoter with opposite transcriptional outputs. PPARα activation enhanced the fatty acid β-oxidation, oxidative phosphorylation (OXPHOS), and adenosine triphosphate (ATP) production, thus promoting proliferation and differentiation of Sox9⁺ hepatocytes along periportal (PP)-perivenous (PV) axis. However, FXR activation increased glycolysis but decreased OXPHOS and ATP production, therefore preventing proliferation of Sox9⁺ hepatocyt

SUBMITTER: Liu S 

PROVIDER: S-EPMC8417399 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature