Exercise suppresses IP6K3 to modulate BCAA metabolism and ferroptosis in MASLD.

ABSTRACT:

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to branched-chain amino acid (BCAA) dysmetabolism and ferroptosis, and exercise is considered protective, yet the underlying mechanisms remain unclear.

Methods

Integrated bioinformatic analyses of public datasets were performed to identify key regulators of MASLD. Hepatic inositol hexakisphosphate kinase 3 (IP6K3) expression was examined in liver samples from patients with MASLD as well as mice. The functional role of IP6K3 was assessed by either hepatocyte-specific Ip6k3 deletion or exercise intervention in mice. Single-cell RNA sequencing (scRNA-seq), IP6K3 overexpression and knockdown, liquid chromatography-tandem mass spectrometry, and co-immunoprecipitation were used to explore the und

SUBMITTER: Li ZC 

PROVIDER: S-EPMC13628866 | biostudies-literature | 2026 Jul

REPOSITORIES: biostudies-literature