The Roles of FGF21 and ALCAT1 in Aerobic Exercise-Induced Cardioprotection of Postmyocardial Infarction Mice.

Aerobic exercise mitigates oxidative stress and apoptosis caused by myocardial infarction (MI) even though the precise mechanisms remain completely elusive. In this study, we investigated the potential mechanisms of aerobic exercise in ameliorating the cardiac function of mice with MI. In vivo, MI was induced by left anterior descending (LAD) coronary artery ligation in wild-type mice, knockout, and knockout mice. The mice were exercised under a moderate-intensity protocol for 6 weeks at one week later post-MI. In vitro, H9C2 cells were treated with lentiviral vector carrying gene, recombinant human FGF21 (rhFGF21), PI3K inhibitor, and HO to explore the potential mechanisms. Our results showed that aerobic exercise significantly increased the FGF21 expression and decreased the ALCAT1 expression in the hearts of mice with MI. knockout weakened the inhibitory effects of aerobic exercise on oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis in mice with MI. Both/either knockout and/or aerobic exercise improved cardiac function by inhibiting oxidative stress and apoptosis in the MI heart. rhFGF21 inhibited both HO and overexpression of ALCAT1-induced oxidative stress and apoptosis by activating the PI3K/AKT pathway in H9C2 cells. In conclusion, our results showed that aerobic exercise alleviated oxidative stress and apoptosis by activating the FGF21/FGFR1/PI3K/AKT pathway or inhibiting the hyperexpression of ALCAT1, which ultimately improved the cardiac function in MI mice.