Aerobic Exercise Inhibits ALCAT1 Expression and Activates FGF21-FGFR1/β-Klotho-PI3K/AKT Pathway to Improve Liver Injury Induced by Myocardial Infarction

Objective: To investigate the role of fibroblast growth factor 21(FGF21) and lysocardiolipinacyltransferase-1(ALCAT1)in improving liver injury induced by myocardial infarction(MI) in mice. Methods: Twenty-four 8-week-old C57/BL6 mice were randomly divided into sham operation group(S), myocardial infarction group(MI) and myocardial infarction exercise group(ME), 8mice in each group. Left anterior descending ligature(LAD) was used to make MI model, and the ME group taken 6-week aerobic training after 1 week of operation. After training, the echocardiography was used to detect the cardiac function and Masson staining was used to detect the myocardial fibrosis. The liver function was evaluated by the activities of AST, ALT and ALP which were detected by kit. Masson and Sirius red staining were used to detect collagen proliferation and TUNEL staining was used to detect hepatocyte apoptosis. The expressions of FGF21, FGFR1, β-Klotho, ALCAT1, endoplasmic reticulum stress(ERs), mitochondrial autophagy and apoptosis related proteins were detected by Western blotting. Results: The CVF% was significantly increased and the cardiac function was significantly decreased in MI group, but the CVF% was significantly decreased and the cardiac function was significantly improved in ME group. Compared with S group, the deposition of liver collagen, AST, ALP, ALT and liver index in MI group were significantly increased(P<0.01, P<0.05), the protein expressions of FGF21, p-PI3K, AKT, ALCAT1, ATF6, IREα,CHOP, GRP78, LC3 Ⅱ/Ⅰ and Bax/Bcl-2 were significantly increased(P<0.05, P<0.01), but the protein expressions of β-Klotho,PINK1, Parkin and P62 were significantly decreased(P<0.01), the TUNEL positive granules was increased significantly(P<0.01).Compared with MI group, the deposition of liver collagen, AST, ALP and ALT in ME group were significantly decreased(P<0.01),and the protein expression of FGF21, FGFR1, β-Klotho, p-PI3K, AKT, PINK1, Parkin and P62 in liver were significantly increased(P<0.05, P<0.01). ALCAT1, ATF6, IREα, CHOP, GRP78 protein expression and LC3 Ⅱ/Ⅰ, Bax/Bcl-2 protein ratio, TUNEL positive granules were decreased significantly(P<0.05, P<0.01). Conclusion: Myocardial infarction can induce endoplasmic reticulum stress, mitochondrial autophagy disorder and hepatocyte apoptosis in the liver, which lead to abnormal liver function.Aerobic exercise downregulates the expression of ALCAT1 and activates FGF21-FGFR1/β-Klotho-PI3K/AKT pathway, inhibit ERstress, mitochondrial autophagy disorder and hepatocyte apoptosis, and improve liver function. It is speculated that FGF21 and ALCAT1 may be important target molecules of aerobic exercise in inhibiting liver injury induced by myocardial infarction.