Hepatic ChREBP reciprocally modulates systemic insulin sensitivity in NAFLD.

ABSTRACT: The relation between hepatic ChREBP level and insulin sensitivity remains equivocal. Our study, however, provides compelling evidence that hepatic ChREBP depletion can significantly enhance insulin sensitivity in high-fat and sucrose-fed mice. We have identified that transcriptional induction of hepatic PTEN is driven by ChREBP. Mechanistically, two critical stimuli are elicited in the hepatic ChREBP knockdown condition. The PTEN level is reduced for one stimulus, thereby promoting hepatic insulin sensitivity. The second stimulus, where reduced hepatic PTEN leads to the enhanced release of FGF21, spreads systemic insulin sensitivity. These findings identify hepatic ChREBP as a critical modulator of systemic insulin signaling and suggest that ChREBP downregulation may lead to protection aga

SUBMITTER: Sen A 

PROVIDER: S-EPMC12155594 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature