Effects Of PPARα On Aerobic Exercise-induced Improvement Of Blood Glucose And Lipid In Obesity,Diabetes And Atherosclerosis Rats And Its Relationship With PPARγ

ObjectNuclear receptor peroxisome-activated receptors(PPAR),including PPARα,PPARβ and PPARγ,play crucial roles in the regulation of glycolipid metabolism,inflammation and cell differentiation,and became research focuses in obesity and obesity-related diseases such as type 2 diabetes and atherosclerosis.Among the three members of PPAR,PPARα is a fatty acid sensor and improves lipid metabolism by regulating the expression of genes involving in metabolisms of fatty acid and lipid,so PPARα is considered as an important target for the treatment of abnormal blood lipid.The common upstream signaling molecule of PPARα is adenosine monophosphate(AMP)-activated protein kinase(AMPK),which exerts an important role in controlling energy metabolisms regardless of cell and organism levels.PPARα downstream molecule carnitine palmitoyl transferase 1(CPT1)is a rate-limiting enzyme for fatty acid oxidation.So activation of AMPK-PPARα-CPT1 signaling pathway can improve lipid metabolism of obesity and obesity-related diseases.Our previous studies have confirmed that PPARγ has an important role in 4-week of aerobic exercise-induced improvement of glycolipid metabolism and alleviation of disease symptoms in the rats with obesity and diabetes,and the effects of PPARγ may be achieved by increasing the protein levels of its target genes such as key enzymes of glycolipid metabolism.Therefore,the purpose of the study was to explore:(1)the effects of AMPK-PPARα-CPT1 pathway in 4-week aerobic exercise-induced improvement of glycolipid metabolism in obesity,diabetes and atherosclerosis rats;(2)the relationship between PPARα and PPARγ in improving glycolipid metabolism in exercised diabetes rats using PPARγ agonist pioglitazone and PPARγ inhibitor GW9662.Methods:One hundred and twenty nine male SD rats age 6-week old were randomly divided into normal diet group(n=12)and high-fat diet group(n=117).Obesity,diabetes and atherosclerosis models rats were established by 8-week high-fat diet,high-fat diet combined with streptozotocin and combined with vitamin D3,respectively.Successful established model rats were randomly divided into 6 groups: obesity(OB),trained obesity(TOB),diabetes mellitus(DM),trained diabetes mellitus(TDM),atherosclerosis(AS)and trained atherosclerosis(TAS),8 rats in each group.In addition,another 16 DM model rats were supplemented with PPARγ agonist pioglitazone or PPARγ inhibitor GW9662 before aerobic exercise,which constituted TDM + pioglitazone group(TDP,n=8)and TDM + GW9662 group(TDG,n=8).All the trained rats had a medium-intensity incremental treadmill training for 4 weeks,once a day and 6 days a week(1st week: 15 m/min speed lasting for 30 min;2nd week: 15 m /min for 60 min;3rd week: 20 m/min for 60 min;4th week: 20 m/min for 90 min).All the rats were fed with ordinary diet during 4-week exercise.The rats were anesthetized and sacrificed at 36 h after the last exercise,and blood,liver,gastrocnemius and perirenal adipose were collected.The protein levels of PPARα,AMPK,CPT1 in the liver,gastrocnemius and perinephric adipose(diabetic rats without perinephric adipose)of the rats were measured by Western blot.The experimental data were analyzed using SPSS23.0 statistical software by one-way ANOVA.Results: 1.Compared with the relative disease rats,the protein levels of PPARα,AMPK,CPT1 were significantly increased in the liver,gastrocnemius and perinephric adipose of TOB,TDM and TAS rats.2.Compared with TDM rats,no significant changes were found in the protein levels of PPARα and CPT1(liver and gastrocnemius)as well as AMPK(liver)of TDG rats although a significant decrease of AMPK was found in gastrocnemius,while the protein levels of PPARα,AMPK and CPT1 were all increased in the liver and gastrocnemius of TDP rats Conclusions: 1.The effect of aerobic exercise on the improvements of blood glucose and blood lipid were related to the up-regulation of AMPK-PPARα-CPT1 signaling pathway in the peripheral metabolic organs of obese,diabetic and atherosclerotic rats.2.Exercise-induced enhancement of PPARα in the liver and gastrocnemius of diabetic rats was independent of PPARγ,while the activation of PPARγ further increased the protein levels of PPARα and its upstream and downstream molecules AMPK and CPT1 in the exercised diabetic rats.