Elevation of hepatic autophagy and antioxidative capacity by endurance exercise is associated with suppression of apoptosis in mice

Abstract

Introduction and objectives: Endurance exercise (EXE) has emerged as a potent inducer of autophagy essential in maintaining cellular homeostasis in various tissues; however, the functional significance and molecular mechanisms of EXE-induced autophagy in the liver remain unclear. Thus, the aim of this study is to examine the signaling nexus of hepatic autophagy pathways occurring during acute EXE and a potential crosstalk between autophagy and apoptosis.

Materials and methods: C57BL/6 male mice were randomly assigned to sedentary control group (CON, n=9) and endurance exercise (EXE, n=9). Mice assigned to EXE were gradually acclimated to treadmill running and ran for 60min per day for five consecutive days.

Results: Our data showed that EXE promoted hepatic autophagy via activation of canonical autophagy signaling pathways via mediating microtubule-associated protein B-light chain 3 II (LC3-II), autophagy protein 7 (ATG7), phosphorylated adenosine mono phosphate-activated protein kinase (p-AMPK), CATHEPSIN L, lysosome-associated membrane protein 2 (LAMP2), and a reduction in p62. Interestingly, this autophagy promotion concurred with enhanced anabolic activation via AKT-mammalian target of rapamycin (mTOR)-p70^S6K signaling cascade and enhanced antioxidant capacity such as copper zinc superoxide dismutase (CuZnSOD), glutathione peroxidase (GPX), and peroxiredoxin 3 (PRX3), known to be as antagonists of autophagy. Moreover, exercise-induced autophagy was inversely related to apoptosis in the liver.

Conclusions: Our findings indicate that improved autophagy and antioxidant capacity, and potentiated anabolic signaling may be a potent non-pharmacological therapeutic strategy against diverse liver diseases.

Keywords: Apoptosis; Autophagy; Endurance exercise; Liver; mTOR.