Fibroblast growth factor 21 protects the heart from apoptosis in a diabetic mouse model via extracellular signal-regulated kinase 1/2-dependent signalling pathway

摘要: This study investigated fibroblast growth factor 21 (FGF21)-mediated cardiac protection against apoptosis caused by diabetic lipotoxicity and explored the protective mechanisms involved. Cardiac Fgf21 mRNA expression was examined in a mouse model using real-time PCR. After pre-incubation of palmitate-treated H9c2 cells primary cardiomyocytes with FGF21 for 15 h, Fgf21-induced cell-survival signalling were small interfering (si)RNA and/or pharmacological inhibitors. We also apoptotic structural functional indices wild-type Fgf21-knockout (Fgf21-KO) mice. In type 1 diabetes, upregulated about 40-fold at 2 months 3–1.5-fold 4 6 months after diabetes. significantly reduced palmitate-induced apoptosis. Mechanistically, palmitate downregulated, but upregulated, phosphorylation levels extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein 14 (p38 MAPK) AMP-activated (AMPK). Inhibition each its inhibitor siRNA revealed that prevents via upregulating ERK1/2-dependent p38 MAPK–AMPK pathway. vivo administration FGF21, not plus ERK1/2 inhibitor, to or fatty-acid-infused mice prevented inactivation ERK1/2, MAPK AMPK remodelling dysfunction. The Fgf21-KO more susceptible diabetes-induced apoptosis, this could be FGF21. Deletion did further exacerbate These results demonstrate lipid- activating ERK1/2–p38 may therapeutic target treatment diabetes-related damage.