FTO-mediated m6A demethylation of BECN1 mRNA promotes hepatic steatosis by impairing autophagy.

ABSTRACT: N6-methyladenosine (m6A) modification plays a critical role in lipid metabolism, yet the mechanism by which the m6A demethylase Fat mass and obesity-associated protein (FTO) regulates hepatic steatosis and autophagy remains unclear. This study aimed to investigate whether FTO modulates lipid metabolism and autophagy through m6A-dependent regulation of Beclin-1 (BECN1). In vitro, HepG2 cells were treated with free fatty acids (FFA) to establish a lipid overload model. Lipid levels were measured enzymatically; autophagy markers were assessed by Western blot; m6A modification was evaluated via dot blot, MeRIP, and RIP assays; and RNA stability was determined using actinomycin D. In vivo, high-fat diet (HFD)-fed mice were established. Liver histology and lipid profiles were analyzed. FFA treat

SUBMITTER: Liu L 

PROVIDER: S-EPMC12750897 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature