Fas apoptotic inhibitor molecule 2 mitigates metabolic dysfunction-associated fatty liver disease through autophagic CRTC2 degradation.

ABSTRACT: Lysosomal membrane proteins play fundamental roles in the lysosomal degradation of proteins and are attractive drug targets for metabolic dysfunction-associated fatty liver disease (MAFLD). Fas apoptotic inhibitory molecule 2 (FAIM2), a lysosomal membrane protein, has been recognized as an inhibitor of apoptosis in a variety of diseases. Here we reveal that FAIM2 is an inhibitor of fatty acid synthesis and suppresses MAFLD. FAIM2 protein expression is decreased in MAFLD. Moreover, FAIM2 is degraded by the E3 ubiquitin ligase NEDD4L through the catalysis of K48-linked ubiquitination. High-fat and high-cholesterol diet-induced hepatic steatosis, inflammation and fibrosis are aggravated in Faim2-knockout mice and alleviated in mice with AAV8-mediated FAIM2 overexpression. Furthermore, in hepa

SUBMITTER: Yu Y 

PROVIDER: S-EPMC12586438 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature