Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation.

ABSTRACT: Metabolic (dysfunction)-associated steatohepatitis (MASH) is the advanced stage of metabolic (dysfunction)-associated fatty liver disease (MAFLD) lacking approved clinical drugs. Adenosine A1 receptor (A₁R), belonging to the G-protein-coupled receptors (GPCRs) superfamily, is mainly distributed in the central nervous system and major peripheral organs with wide-ranging physiological functions; however, the exact role of hepatic A₁R in MAFLD remains unclear. Here, we report that liver-specific depletion of A₁R aggravates while overexpression attenuates diet-induced metabolic-associated fatty liver (MAFL)/MASH in mice. Mechanistically, activation of hepatic A₁R promotes the competitive binding of sterol-regulatory element binding protein (SREBP) cl

SUBMITTER: Zhu W 

PROVIDER: S-EPMC10983109 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature