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

ObjectiveTo investigate the effects of different exercise programs on high-fat-diet induced non-alcoholic fatty liver disease(NAFLD)in rats.MethodsSix-week-old SD rats were randomly assigned to:(1)sedentary rats fed with normal diet group(C group);(2)sedentary rats fed with high-fat diet group(H group);(3)sedentary rats fed with high-fat diet group 1(H1 group);(4)high-fat diet rats swimming 60-min per day from 1 to 12 week(HE60-1 group);(5)high-fat diet rats swimming 90-min per day from 1 to 12 week(HE90-1 group);(6)sedentary rats fed with high-fat diet group 2(H2 group);(7)high-fat diet rats swimming 60-min per day from 13 to 20 week(HE60-2 group);(8)high-fat diet rats swimming 90-min per day from 13 to 20 week(HE90-2 group).Rats fed with high-fat diet for 12 weeks to induce NAFLD.The protein provided 22%,fat 38%and carbohydrate 40%of total energy(4243Kcal/1000g)intake.Comprehensive using body weight,liver index,blood lipid,liver lipid and liver function to evaluate the animal model of NAFLD and the effects of exercise intervention.Observing the impacts of high-fat feeding and exercise on FFA,blood lipids.Adopting real-time PCR to determine the mRNA expression of PPAR-??SREBP-lc?SCD-1,and using Western blot to detect the protein expression of pAktSer473,AMPK,Ak,PPAR-a?SREBP-1c?SCD-1,respectively,to investigate the effects of different swimming exercise programs on NAFLD in liver of high-fat-diet rats as well as some mechanisms.Results1.To evaluate NAFLD animal modelAfter 12 weeks,to compared with C group,the body weight,liver weight,and liver index of H group were dramatically increased(p<0.01),the level of serum FFA?TC?TG?LDL-C of H group were obviously increased(p<0.01),the level of liver TC,TG,ALT and AST of H group were also markedly increased(p<0.01).Morphologically,the liver began turn to light yellow,the liver was bigger and more hypertrophic,much lipid left on the blade.In conclusion,it was considered to become NAFLD.2.Effect of different exercise programs on high-fat-diet induced NAFLD in rats(1)After 12 weeks,to compared with H1 group,the body weight,liver weight,and liver index of group HE60-1 and HE90-1 were dramatically decreased(p<0.05),the level of serum FFA?TC?TG?LDL-C of HE60-1 and HE90-1 group were obviously decreased(p<0.05 or p<0.01),the level of liver TC,TG,ALT and AST of H group were also markedly decreased(p<0.01).But there were no differences between HE60-1 and HE90-1 group.It suggested that both swimming exercise for 60min and swim exercise 90min for 12 weeks can ameliorate high-fat-diet induced NAFLD in rats.(2)After 8-week to treat NAFLD,to compared with H2 group,the body weight,liver weight,and liver index of group HE60-2 and HE90-2 were dramatically decreased(p<0.05),the level of serum FFA?TC?TG?LDL-C of HE60-2 and HE90-2 group were obviously decreased(p<0.05 or p<0.01),the level of liver TC,TG,ALT and AST of H group were also markedly decreased(p<0.01).But there were also no differences between HE60-2 and HE90-2 group.It suggested that both swimming exercise for 60min and swim exercise 90min for 8 weeks can ameliorate NAFLD effectively.3.The mechanism of different swimming exercise program on preventing NAFLD in liverAfter 12 weeks,(1)to compared with H1 group,morphologically,the liver is beige,the liver was smaller and less lipid left on the blade in the HE60-1 group;and in HE90-1 group,the live is similar to the normal liver both on morphology and color,and without lipid left almost.(2)to compared with H1 group,the protein expression of pAktSer473 and AMPK in liver of group HE60-1 and HE90-1 were dramatically increased(p<0.05 or p<0.01),the mRNA and protein expression of liver SREBP-lc?SCD-1 were obviously decreased(p<0.05 or p<0.01),while the mRNA and protein expression of liver PPAR-a were obviously increased(p<0.01).4.The mechanism of different swimming exercise program on treating NAFLDAfter 8-week swimming,(1)to compared with H2 group,morphologically,the liver was smaller and few lipid left on the blade in the HE60-2group;and in HE90-2 group,the live is similar to the liver in group C,the color is close to red,the size is much smaller,and without lipid left almost.(2)to compared with H2 group,the protein expression of pAktSer473 and AMPK in liver of group HE60-2 and HE90-2 were dramatically increased(p<0.05 or p<0.01),the mRNA and protein expression of liver SREBP-1c?SCD-1 were obviously decreased(p<0.05 or p<0.01),however,the mRNA and protein expression of liver PPAR-a were obviously increased(p<0.05,p<0.01).Conclusions1.12-week high-fat feeding is prone to induce NAFLD model in rat.2.Both swim exercise 60 min and 90min per day for 12 weeks can ameliorate high-fat-diet induced NAFLD in rats.But the effect of the two exercise program on preventing high-fat-diet induced NAFLD has no difference3.Both swim exercise 60 min and 90min per day for 8 weeks can traeting high-fat-diet induced NAFLD effectively.But the effect of the two exercise program on curing high-fat-diet induced NAFLD show no difference.4.The mechanisms of swimming exercise on ameliorating NAFLD may be:(1)Swimming exercise can enhance the PI3-K/Akt signaling transduction,then activate the AMPK signal pathway,which can directly inhibit the expression of PPAR-a and/or SREBP-1c,thus ameliorate high-fat-diet induced NAFLD in rats though accelerating the lipid metabolism.(2)Swimming exercise can enhance the PI3-K/Akt signaling transduction,then activate the AMPK signal pathway,then inhibit the expression of mTOR,which can indirectly influence the lipid metabolism:when the expression of mTOR was down-regulated,on one hand,the lipid metabolism could turn to rapid through up-regulating the expression of PPAR-a;furthermore,the down-regulated level of mTOR could inhibit the expression of SREBP-lc and SCD-1,then result to reduce the lipid synthesis.