Effect Of Different Exercise Programs On High-fat-diet Induced Insulin Resistance In Rats

ObjectiveTo investigate the effects of different exercise programs on high-fat-diet induced insulin resistance in rats.MethodsSix-week-old SD rats were randomly assigned to6groups:(1) sedentary rats fed with normal diet group (C group);(2) normal diet rats swimming1time per day(successive90min/time)(CEA group);(3) normal diet rats swimming twice per day(successive45min/time)(CEB group);(4) sedentary rats fed with high-fat diet group (H group);(5) high-fat diet rats swimming1time per day(successive90min/time)(HEA group);(6) high-fat diet rats swimming2time per day(successive45min/time)(HEB group). Rats of H group were fed with high-fat diet for8weeks to induce insulin resistance (IR). The protein provided22%, fat38%and carbohydrate40%of total energy (4243Kcal/1000g) intake. Rats in CEA group and HEA group took swim exercise1time per day(successive90min/time), rats in CEB group and HEB group took swim exercise twice per day(successive45min/time), rats in the four groups were all swam6days for8weeks. Comprehensive using body weight, FBG, FINS, HOMA-IR, ISI and he euglycemic-hyperinsulinemic clamp experiments to evaluate the animal model of IR and effects of exercise intervention. Observing the impacts of high-fat feeding and exercise on FFA, blood lipids, visceral fat, and skeletal muscle lipids deposition. Adopting real-time PCR, ELISA and Western blot to observe the mRNA expression of PGC-la, FAT/CD36, MG53, Cav-3, IRS-1, the contents of CRP, TNF-a, IL-6, INF-y, and the protein expression of MG53, IRS-1, Akt in skeletal muscle respectively, to investigate the effects of different swimming exercise programs on insulin resistance in skeletal muscle of high-fat-diet rats as well as some mechanisms. Adopting real-time PCR, ELISA and Western blot to observe the mRNA expression of IRS-1, the contents of TNF-a, and the protein expression of IKKβ, JNK, IRS-1, Akt in adipose tissue respectively, To investigate the effect of different swimming exercise program on insulin resistance in adipose tissue of high-fat-diet rats as well as some mechanisms.Results1. To evaluate IR animal model:After8weeks, to compared with C group, the level of insulin and HOMA-IR of H group were dramatically increased (p<0.01), the level of ISI and GIR of H group were markedly decreased (p<0.01). It was considered to become IR.2. Effect of different exercise programs on high-fat-diet induced Insulin resistance in rats:After8weeks, to compared with H group, the level of INS and HOMA-IR of HEA group were dramatically decreased (p<0.05), the level of ISI and GIR and HDL-C of HEA group were obviously increased (p<0.01). the level of INS and HOMA-IR of HEB group were dramatically decreased (p<0.01), the level of ISI and GIR and HDL-C of HEB group were obviously increased (p<0.01). But there were no differences between HEA and HEB group. It suggested that both swim exercise1time per day (successive90min/time) and swim exercise twice per day (successive45min/time) for8weeks can ameliorate high-fat-diet induced insulin resistance in3. The effect of different swimming exercise program on insulin resistance in skeletal muscle:①The visceral fat mass and the lipid deposits in skeletal muscle:After8weeks, to compared with H group, the visceral fat mass and the abdominal fat index in both HEA and HEB group were obviously decreased (p<0.01), but there were no differences between HEA and HEB group. both in HEA group and HEB group the level of FFA and TG were dramatically decreased (p<0.01), the mRNA expression of PGC-la and FAT/CD36were also markedly decreased (p<0.01). It suggested that both swim exercise1time per day (successive90min/time) and swim exercise twice per day (successive45min/time) for8weeks can reduce lipid deposits in skeletal muscle in high-fat-diet rat. But the effects of the two exercise programs have no differences.②The mRNA and protein expression of MG53in skeletal muscle:After8weeks, to compared with H group, the mRNA and protein expression of MG53were markedly decreased (p<0.01) both in HEA group and HEB group. But there were no differences between HEA and HEB group. It suggested that both swim exercise1time per day (successive90min/time) and swim exercise twice per day (successive45min/time) for8weeks can reduce the expression of MG53in skeletal muscle in high-fat-diet rat. But the effects of the two exercise programs have no differences.③Ceramide and inflammatory factor in skeletal muscle:After8weeks, to compared with C group, the content of Ceramide and inflammatory factor (CRP、TNF-α、IL-6and INF-y) were significantly increased (p<0.05or p<0.01) of H group; to compared with H group, the content of Ceramide and inflammatory factor (CRP、TNF-α、IL-6and INF-y) were significantly were obviously reduced (p<0.05or p<0.01) both in HEA group and HEB group. But there were no differences between HEA and HEB group. It suggested that both swim exercise1time per day (successive90min/time) and swim exercise twice per day (successive45min/time) for8weeks can decrease the level of Ceramide and inflammatory factor in skeletal muscle in high-fat-diet rat. But the effects of the two exercise programs have no differences.④The mRNA expression of Cav-3, the level of eNOS and GLUT4in skeletal muscle:After8weeks, to compared with H group, the mRNA expression of Cav-3, content of eNOS and GLUT4in skeletal muscle both in HEA group and HEB group were significantly decreased (p<0.05or P<0.01). But there were no differences between HEA and HEB group. It suggested that both swim exercise1time per day (successive90min/time) and swim exercise twice per day (successive45min/time) for8weeks can decrease the level of Cav-3, eNOS and GLUT4in skeletal muscle in high-fat-diet rat. But the effects of the two exercise programs have no differences.⑤The expression of IRS-1and Akt in skeletal muscle:After8weeks, to compared with H group, the mRNA and protein expression of IRS-1, pAktSer473and Akt of skeletal muscle both in HEA group and HEB group were dramatically increased (p<0.05or p<0.01), the protein expression of pIRS-1Ser307was obviously decreased (p<0.01). But there were no differences between HEA and HEB group. It suggested that both swim exercise1time per day (successive90min/time) and swim exercise twice per day (successive45min/time) for8weeks can increase the level of IRS-1and Akt of skeletal muscle in high-fat-diet rat. But the effects of the two exercise programs have no differences.4. The effect of different swimming exercise program on insulin resistance in adipose tissue:①The level of FFA, TNF-α, IKKβ and JNK in adipose tissue:After8weeks, to compared with H group, the content of FFA and TNF-α in adipose tissue of H group were dramaticlly decreased (p<0.01) both in HEA and HEB group, the protein expression of IKK β pJNKThr183/Tyr185and JNK were markedly decreased (p<0.01) both in HEA and HEB group. But there were no differences between HEA and HEB group. It suggested that both swim exercise1time per day (successive90min/time) and swim exercise twice per day (successive45min/time) for8weeks can decrease the level of FFA, TNF-α, IKKβ and JNK in adipose tissue in high-fat-diet rat. But the effects of the two exercise programs have no differences.②The mRNA and protein expression of IRS-1and Akt in adipose tissue:After8weeks, to compared with H group, the mRNA and protein expression of IRS-1, pAktSer473and Akt of adipose tissue both in HEA group and HEB group were dramatically increased (p<0.05or p<0.01), the protein expression of pIRS-1Ser307was obviously decreased (p<0.01). But there were no differences between HEA and HEB group. It suggested that both swim exercise1time per day (successive90min/time) and swim exercise twice per day (successive45min/time) for8weeks can increase the level of IRS-1and Akt of adipose tissue in high-fat-diet rat. But the effects of the two exercise programs have no differences. Conclusion1.8-week high-fat feeding is prone to induce IR model in rat.2. Both swim exercise1time per day (successive90min/time) and swim exercise twice per day (successive45min/time) for8weeks can ameliorate high-fat-diet induced insulin resistance in rats. But the effect of the two exercise program on ameliorate high-fat-diet induced insulin resistance in rats has no difference.3. The action mechanisms of swimming exercise on ameliorating skeletal muscle IR may through four pathways——Swimming exercise can ameliorate high-fat-diet induced skeletal muscle IR in rats through reducing lipid deposits, decreasing the mRNA and protein expression of MG53, making a decline on the level of inflammatory factors, improve the expression of Cav-3, then enhancing the PI3-K/Akt signaling transduction, thus ameliorate high-fat-diet induced skeletal muscle insulin resistance in rats.The action mechanisms of swimming exercise on ameliorating adipose tissue IR may be: swimming exercise can make IRS-1/PI3-K/Akt signaling transduction enhancement through inhibit inflammatory signaling pathways (IKKβ/NF-κB and JNK/SAPK), thus ameliorating high-fat-diet induced adipose tissue insulin resistance in rats.