Somatic loss-of-function mutations in CIDEB reduce hepatic steatosis by increasing lipolysis and fatty acid oxidation.

ABSTRACT:

Background & aims

Somatic and germline CIDEB mutations are associated with protection from chronic liver diseases. The mechanistic basis and whether CIDEB suppression would be an effective therapy against fatty liver disease remain unclear.

Methods

21 CIDEB somatic mutations were introduced into cells to assess functionality. In vivo screening was used to trace Cideb mutant clones in mice fed normal chow, western (WD), and choline-deficient, L-amino acid-defined, high-fat (CDA-HFD) diets. Constitutive and conditional Cideb knockout mice were generated to study Cideb in liver disease. Isotope tracing was used to evaluate fatty acid oxidation and de novo lipogenesis. Transcriptomics, lipidomics, and metabolic analyses were utilized to explore molecular mechanisms. Double knock

SUBMITTER: Zeng Q 

PROVIDER: S-EPMC12313214 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature