FGF21 attenuates sepsis-induced myocardial injury via AMPK-mediated mitochondrial biogenesis.

Abstract

Sepsis is a life-threatening infection that often leads to myocardial injury. Here we explored the role of fibroblast growth factor 21 (FGF21) in sepsis-induced myocardial injury and its underlying mechanism. A mouse model of sepsis-associated myocardial injury was established by cecal ligation and puncture (CLP). Serum FGF21 levels were upregulated in CLP mice (sham: ∼300 pg/mL; CLP: ∼420 pg/mL). CLP led to myocardial injury, inflammation, and apoptosis. Cardiac-specific overexpression of FGF21 via AAV9-cTnT improved 5-day survival rate from ∼20% (CLP) to ∼60% (CLP + OE-FGF21), reduced histological damage, suppressed apoptosis, and upregulated p-AMPK/AMPK and PGC-1α. In LPS-treated H9C2 cells, FGF21 overexpression reversed the LPS-induced decline in mitochondrial function. The AMPK agonist AICAR mimicked, while the AMPK antagonist Compound C partially reversed, the protective effects of FGF21. In conclusion, FGF21 overexpression alleviates sepsis-associated myocardial injury by restoring mitochondrial function via AMPK/PGC-1α pathway.