A Somatic Mutation in HIF-2α Affects Glucose and Lipid Metabolism via CD36 and Ceramide.

ABSTRACT: Hypoxia-inducible factor 2α (HIF-2α) plays a critical role in metabolic regulation. Previously, our team identified a novel mutation (c.C2473T, p.R825W) within the C-terminal transactivation domain of HIF-2α, which was associated with the pathogenesis of non-alcoholic fatty liver disease. The present study aimed to investigate the relationship between this mutation and disorders of glucose and lipid metabolism, and to elucidate the underlying mechanisms. A HIF-2α mutant C56BL/6 mouse model and THLE-2 and HEK293 cell lines carrying the same mutation were established. Co-immunoprecipitation and western blot were used to assess the molecular effects of the mutation. Transcriptome sequencing, quantitative real-time PCR, and western blotting were performed to identify differentially expressed g

SUBMITTER: Gao F 

PROVIDER: S-EPMC12752453 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature