SLC13A2 promotes hepatocyte metabolic remodeling and liver regeneration by enhancing de novo cholesterol biosynthesis.

ABSTRACT: Metabolic requirements of dividing hepatocytes are prerequisite for liver regeneration after injury. In contrast to transcriptional dynamics during liver repair, its metabolic dependencies remain poorly defined. Here, we screened metabolic genes differentially regulated during liver regeneration, and report that SLC13A2, a transporter for TCA cycle intermediates, is decreased in rapid response to partial hepatectomy in mice and recovered along restoration of liver mass and function. Liver-specific overexpression or depletion of SLC13A2 promoted or attenuated liver regeneration, respectively. SLC13A2 increased cleavage of SREBP2, and expression of cholesterol metabolism genes, including LDLR and HMGCR. Mechanistically, SLC13A2 promotes import of citrate into hepatocytes, serving as building

SUBMITTER: Shi L 

PROVIDER: S-EPMC11876347 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature