| Background:sarcopenia is a muscular dystrophy syndrome characterized by age-related decline in muscle mass,strength and function,which is often accompanied by metabolic diseases such as obesity and diabetes.However,the molecular mechanism of the relationship between metabolic diseases and skeletal muscle atrophy is not fully understood.It has been found that PARK7 can positively regulate the PI3K/AKT signal pathway to promote myotube hypertrophy and maintain blood glucose homeostasis by inhibiting the expression of PTEN.Objectives: Taking PARK7/PTEN/AKT signal pathway as a starting point,this paper discusses how exercise regulates the molecular mechanism of glucose metabolism and skeletal muscle atrophy in aging and high-fat diet of organism,so as to provide insights and theoretical basis for exercise to improve sarcopenia and metabolic diseases such as obesity and diabetes.However,whether exercise regulates glucose metabolism disorders and skeletal muscle atrophy in aging and high-fat diet of organism through PARK7/PTEN/AKT signal pathway remains to be further explored.Methods: Under standard feeding conditions,25 5-week-old BALB/c healthy male mice were fed to 52 weeks of age to establish a natural aging model,and then randomly divided into normal diet group(group C,n = 6),high-fat diet group(CH group,n = 6),resistance exercise high-fat diet group(RH group,n= 6)and resistance combined with aerobic exercise high-fat diet group(RAH group,n = 7).The exercise group intervened with high-fat diet and exercise for eight weeks.Among them,the resistance exercise adopts tail weight-bearing ladder resistance training,and aerobic exercise adopts weight-free treadmill training.Their body weight and dietary status were recorded weekly during the intervention.The weekly exercise training schedule was make timely adjustment according to the maximum load measured by each mouse each week.The glucose tolerance test was carried out 12 hours after the last training,and then dissected and sampled.The protein expression levels of PARK7,PTEN,P-AKT,FOXO1,P-FOXO1,Myostatin and GLUT4 in quadriceps femoris were detected by Wes TM automatic protein expression analysis system.The fiber size of quadriceps femoris was observed by Hematoxylin-eosin staining technique and the status of inguinal fat(i WAT)tissue droplets was detected by oil red staining.SPSS23,Graph Pad Prism8.0 and Image J software were used for data statistics and mapping,and paired sample t-test and one-way ANOVA were used to analyze the experimental data.Results:(1)The changes of body weight,muscle wet weight / body weight: compared with those before the experiment,the body weight of exercise group and non-exercise group decreased significantly after the end of the experiment,especially in group C and RAH(P<0.05).During the experiment,the body weight of the exercise group(RH and RAH groups)increased in the first two weeks and decreased gradually in the last six weeks.The body weight of the non-exercise group(C,CH group)showed a downward trend throughout the experiment,in which the weight loss was more obvious in the first four weeks.There was no significant difference between the wet weight of quadriceps femoris and quadriceps femoris / body weight.(2)Comparison of cross-sectional area of quadriceps femoris fiber after experiment: compared with exercise group(RH and RAH group),non-exercise group(C,CH group)quadriceps femoris fiber is looser,especially CH group shows larger muscle fiber space,while exercise group RH group muscle fiber is more compact.The cross sectional area of quadriceps femoris in CH group was significantly smaller than that in C group(P < 0.05)and extremely significantly smaller than RH group(P < 0.001)and RAH group(P < 0.01),but there was no significant difference between exercise groups.(3)The changes of muscle strength before and after the experiment: the absolute grip strength of the four groups showed a downward trend.The absolute grip strength of group C(P < 0.05),group CH(P<0.01)and group RAH(P < 0.05)decreased significantly,and that of CH group was significantly lower than that of RAH group(P < 0.05).There was no significant difference between C group,RH group and RAH group.After the experiment,the relative grip strength of RH group and RAH group was significantly higher than that before experiment(P < 0.05),while that of C group and CH group decreased,and that of CH group was significantly lower than that of RH group(P < 0.05)and RAH group(P < 0.05).(4)Comparison of mouse glucose tolerance: the blood glucose value of mice in each group increased rapidly within 15 minutes after injection of glucose solution,and then began to decrease,in which the blood glucose value in the CH group was the highest at 15 minutes,and significantly higher than that in the RAH group(P < 0.05).The blood glucose level of CH group was significantly higher than that of RH group and RAH group at 60min(P < 0.05),but did not return to the initial level at 120 min and was significantly higher than that of RAH group(P < 0.05).The area under the glucose tolerance curve of each group also showed that the glucose tolerance of aged mice in CH group was significantly lower than that in RH group and RAH group(P <0.05).(5)Inguinal fat(i WAT)tissue droplets: the weight of inguinal white fat in the non-exercise group was larger than that in the exercise group,and the accumulation of inguinal white fat in the CH group was significantly higher than that in the RAH group(P < 0.05),CH group was larger than C group,but there was no significant difference.Oil red staining showed that the lipid droplet distribution of i WAT in CH group was significantly higher than that in C group(P < 0.05),and extremely significantly larger than that in RH group(P< 0.01)and RAH group(P < 0.001).(6)PARK7 and PTEN protein expression: the expression of PARK7 protein in quadriceps muscle in exercise group(RH and RAH group)was significantly higher than that in CH group(P < 0.05),but there was no significant difference between exercise group and C group.The expression of PTEN protein in quadriceps femoris in CH group was higher than that in C group and significantly higher than that in RH group(P < 0.05)and RAH group(P <0.05).There was no significant difference in the expression of PTEN protein in quadriceps femoris between group C and RH and RAH.(7)P-AKT and FOXO1 protein expression and phosphorylation level: the AKT phosphorylation level of quadriceps femoris in group C was significantly lower than that in RAH group(P < 0.05),but not significantly different from that in RH group,and that in CH group was significantly lower than that in RH group and RAH group(P < 0.01).The expression of FOXO1 protein in quadriceps femoris in RH group and RAH group was significantly lower than that in CH group(P < 0.05),while the phosphorylation level of FOXO1 in quadriceps femoris in RH group and RAH group was significantly higher than that in C group(P < 0.05)and extremely significantly higher than CH group(P< 0.01).(8)Myostatin and GLUT4 protein expression: the expression of Myostatin protein in quadriceps femoris in RH group and RAH group was extremely significantly lower than that in CH group(P < 0.01)and C group,and that in RAH group was significantly lower than that in C group(P < 0.05).There was no significant difference in the expression of GLUT4 protein in quadriceps femoris between group C and RH and RAH.The expression of GLUT4 protein in quadriceps femoris in RH group and RAH group was significantly higher than that in CH group(P < 0.05),but there was no significant difference between RH group and RAH group.Conclusions:(1)Resistance exercise and resistance combined with aerobic exercise can maintain the stability of body weight and slow down the decrease of cross-sectional area of muscle fiber in aged mice with high-fat diet,and effectively improve their relative strength.(2)Resistance exercise and resistance combined with aerobic exercise may up-regulate the expression of GLUT4 protein through PARK7/PTEN/AKT signal pathway to improve the level of glucose tolerance in aged mice fed with high-fat diet,thus regulating the homeostasis of glucose metabolism.(3)Resistance exercise and resistance combined with aerobic exercise may increase the level of FOXO1 phosphorylation and down-regulate the expression of Myostatin through PARK7/PTEN/AKT signal pathway,thus slow down the process of skeletal muscle atrophy in aged mice fed with high-fat diet. |
PDF Full Text Request