FGF9 alleviates diabetic cardiomyopathy by activating Nrf2 via SQSTM1/p62-Keap1 in mice.

ABSTRACT: Fibroblast growth factor 9 (FGF9) plays a key role in development and cardioprotection, yet its function in diabetic cardiomyopathy (DCM) remains unclear. In a high-fat diet/streptozotocin (HFD/STZ)-induced DCM model, FGF9 attenuated cardiac hypertrophy, fibrosis, and systolic dysfunction, effects abolished in cardiomyocyte-specific Nrf2 knockout mice. Mechanistically, FGF9 restored AMPK activity and promoted autophagy, enhancing p62-mediated degradation of Keap1 and nuclear translocation of Nrf2. In neonatal rat cardiomyocytes (NRCMs), FGF9 reversed high glucose and palmitate (HG + PA)-induced suppression of AMPK phosphorylation, autophagic flux, and Nrf2 signaling. AAV9-mediated expression of wild-type AMPK (AMPK^WT) or a dominant-negative AMPK mutant (AMPK^T172A) con

SUBMITTER: An N 

PROVIDER: S-EPMC12647667 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature