Hepatic E4BP4 induction promotes lipid accumulation by suppressing AMPK signaling in response to chemical or diet-induced ER stress.

ABSTRACT: Prolonged ER stress has been known to be one of the major drivers of impaired lipid homeostasis during the pathogenesis of non-alcoholic liver disease (NAFLD). However, the downstream mediators of ER stress pathway in promoting lipid accumulation remain poorly understood. Here, we present data showing the b-ZIP transcription factor E4BP4 in both the hepatocytes and the mouse liver is potently induced by the chemical ER stress inducer tunicamycin or by high-fat, low-methionine, and choline-deficient (HFLMCD) diet. We showed that such an induction is partially dependent on CHOP, a known mediator of ER stress and requires the E-box element of the E4bp4 promoter. Tunicamycin promotes the lipid droplet formation and alters lipid metabolic gene expression in primary mouse hepatocytes from E4bp4<

SUBMITTER: Yang M 

PROVIDER: S-EPMC8011030 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature