Effects of HIIT on Oxidative Stress in the Skeletal Muscle of ApoE-/-Mice Fed with a High-fat Diet and the Protective Effects of BAIBA
Objective:To investigate the effects of high-intensity interval training(HIIT)on oxidative stress in the skeletal muscle of ApoE-/-mice fed with a high-fat diet,and the possible regulatory mechanism of β-aminoisobutyr-ic acid(BAIBA)in these effects.Methods:9-week-old healthy male C57BL/6J and ApoE-/-mice were fed a standard or high-fat diet,respectively.C57BL/6J mice were the baseline control group(WT,n=6),and ApoE-/-mice were randomly assigned to sedentary(ApoE-/-,n=10)and HIIT(ApoE-/-HIIT,n=10)groups after 12 weeks of high-fat feeding.The ApoE-/-HIIT group received 6 weeks of HIIT,WT and ApoE-/-groups received no intervention.Forty-eight hours after the last exercise session,the whole gastrocnemius muscle of both hind limbs of the mice were taken for the detection of oxidative damage,antioxidant,and BAIBA production-related indicators.In vitro experiment,C2C12 cells were pre-incubated with L-BAIBA,and then oxidative stress was induced with hydro-gen peroxide(H2 O2).Combined with the intervention,they were randomly divided into Control,H2 O2 and L-BAIBA+H2O2 groups,then the cell morphology,ROS level and related indicators of Nrf2-mediated antioxidant pathways were determined.Results:1)Compared with the WT group,ApoE-/-mice increased the expression of 4-HNE modified protein,protein carbonylation content and ROS level,while decreased the protein expression of p-Nrf2 and the concentration of GSH in the skeletal muscle.Compared with the ApoE-/-group,HIIT significantly de-creased the expression of 4-HNE modified protein,protein carbonylation content,while increased the protein ex-pression of p-Nrf2 and the concentration of GSH.2)The mRNA expression of Acads and Hadha related to the pro-duction of BAIBA in the skeletal muscle of mice in the ApoE-/-HIIT group were significantly higher than those in the ApoE-/-group.3)Compared with the Control group,C2C12 cells in the H2O2 group shrank significantly,the number of viable cells decreased,and the level of ROS increased under the stimulation of H2 O2 oxidative stress.While the morphology,number and ROS level of viable cells were significantly improved in the L-BAIBA+H2O2 group compared with the H2O2 group.4)Compared with the Control group,the protein expression of Nrf2,p-Nrf2 and their mediated antioxidant enzymes SOD1,NQO1,CAT,as well as the mRNA expression of Gss,Gsr,Gclm related to GSH synthesis and the concentration of GSH in the H2O2 group were significantly decreased.While L-BAIBA preincubation increased the protein expression of p-Nrf2,SOD1,NQO1 and the mRNA expression of Gss、Gsr、Gclc,Gclm,as well as the concentration of GSH in the C2C12 cells under the stimulation of H2O2.Conclu-sion:6-week HIIT can ameliorate oxidative damage in the skeletal muscle of ApoE-/-mice fed with a high-fat diet,in which the activation of Nrf2-mediated antioxidant signaling by the myokine of BAIBA may play an important role.
万方数据
维普
