HNF4α contributes to hepatic CAR dysfunction in polymicrobial sepsis.

ABSTRACT: The constitutive androstane receptor (CAR), encoded by the Nr1i3 gene, is a nuclear receptor mainly expressed in the liver, where it regulates (xenobiotic) drug and bile acid metabolism, bilirubin clearance and energy homeostasis. CAR has emerged as a promising therapeutic target for diabetes, fatty liver disease and alcoholic liver disease, but it has barely been investigated in the context of sepsis. Since alterations in drug metabolism have been observed in sepsis patients, who may also exhibit increased serum bilirubin and bile acid levels, we hypothesize that CAR function may be impaired during sepsis. Here, we demonstrate that CAR loses its function in the liver during sepsis, as evidenced by a diminished response to its agonist TCPOBOP. We show that Nr1i3 mRNA transcri

SUBMITTER: Van Dender C 

PROVIDER: S-EPMC12401704 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature