The Effect of Endurance Exercise on Autophagy and Mitophagy in the Skeletal Muscle of Mice with Alimentary Obesity

Objective:To determine the effect of endurance exercise on cellular autophagy and mitophagy in skeletal muscle of obese mice and explore the underlying molecular mechanism.Methods:After the alimentary obesity ICR mice modle constrction, the obese mice were randomly divided into high-fat diet control group (HC, n=6) , normal diet amelioration group (HN, n=6) and normal diet combined with endurance exercise group (HNE, n=6) .The mice of normal diet control group during the constrction of alimentary obesity model were assigned as the normal control group (NC, n=6) .The mice in groups NC, HN and HNE were fed with nomal diet while the mice of group HC were fed with high-fat diet.The mice of group HNE underwent treadmill running for 6weeks, 45min/d, 6times per week.Results:1) High-fat dier for 6week increased the body weight, Lee's index and epididymal fat percentage of mice, while a series of blood index such as BG, TG, TC, HDL-C and LDL-C increased significantly.2) The relative contents of myosin heavy chain Ⅰ, Ⅱa and Ⅱc mRNA were upregulated in group HNE, compared with group HC.3) The mitochondrial membrance potential of skeletal muscle in group HC was lower than that of group NC, while the mtDNA relative content in group HC, HN and HNE were lower than NC.4) Compared to NC, the autophagy related genes ATG13 and LC3 mRNA decreased while P62 mRNA expression level increased;the BECN1, ATG13 and LC3mRNA relative content of HN and HNE were higher than those in HC (P<0.05) and the ratio of LC3Ⅱ/Ⅰof HNE increased in skeletal muscle compared with HC.5) The mitophagy related gene NIX mRNA expression was lower in HC compared to that of NC, whereas it accerlarated in group HN and HNE;in group HNE, the PARK2 and PARL mRNA relative content increased compared to HN;the protein content of PINK1 downregulated in HC and up-regulated obviously in group HN and HNE (P<0.05) .Conclusion:1) Long-term high-fat-diet intervention can lead to alimentary obesity accompanied with metabolic disorders and mitochondrial dysfunction in the skeletal muscle.2) Endurance exercise combined with dietary intervention can effectively slow down the weight gain and increase the protein expression of myosin heavy chain in the alimentarily obese mice.3) Endurance exercise combined with dietary intervention can obviously attenuate the decline of autophagy level induced by high-fat-diet as well as maintain the quality and function of mitochondria in skeletal muscle, in which the mitophagy related PINK1/Parkin singnaling pathway involves and plays a crititial role.