The AKAP12-PKA axis regulates lipid homeostasis during alcohol-associated liver disease.

ABSTRACT: Disrupted lipogenic signaling and steatosis are key features of alcohol-associated liver disease (ALD). A-kinase anchoring protein 12 (AKAP12) is a scaffolding partner of the cAMP-dependent protein kinase, PKA that controls its spatiotemporal localization. Activation of PKA by cAMP inhibits lipogenesis and facilitates fatty acid oxidation (FAO). The goal of this work is to examine how AKAP12's PKA-anchoring ability regulates outcomes of alcohol-associated steatosis. Crosslinking proteomics identified PKA and its lipogenic substrates as interacting partners of AKAP12. Alcohol exposure diminished AKAP12's interaction with PKA regulatory subunits and PKA substrates, acetyl CoA carboxylase (ACC1), pyruvate dehydrogenase (PDHA) and adipose triglyceride lipase (ATGL). Alcohol inhibited PKA activ

SUBMITTER: Thimme Gowda C 

PROVIDER: S-EPMC11979000 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature