The Impact Of Different Interventions On Ectopic Lipid Deposition And Expression Of FAT/CD36in Skeletal Muscle Of Obese Rats Fed With High-fat Diet

BackgroundWith the accelerating rise of obese morbidity in both adults and children,we arefacing a series of severe social problems of worldwide.Obesity always accompanied byhigh serum glucose, hyperlipidemia and eventually metabolism syndrome.The mostfundamental physiopathologic links of metabolism syndrome is insulin resistance,themain reason of which is central obesity. Recent study shows that hyperlipidemia cancause excessive TG deposit in pancreatic beta cell, skeletal muscle cell and hepatocyte,which impair the normal function of these organs, leading to insulin resistance. Skeletalmuscle as the main effect tissue of insulin, plays an essential role in the body’sresistance to insulin.As is known to all,dietary control,aerobic exercise and metformincan reduce weight and improve insulin sensitivity,but the true effect and mechanismremain to be determined. In this study we try to observe the excessive cellulardeposition of TG mainly in skeletal muscle tissue in SD rats with high-fat diet,and theimpact of different interventions on lipid metabolism with insulin resistance.Objective To establish nutritional obesity model of male Sprague-Dawley rat byhigh-fat diet for18weeks for observing the effect of skeletal muscle fatty ectopicdeposition and FAT/CD36protein expression caused by lipotoxcity and differentinterventions,in order to preliminarily investigate the relationship of excessivedeposition of TG and insulin resistance in skeletal muscle. Methods60healthy male SD rats of four weeks age were randomly divided into normalcontrol group(NC group,n=10) and high-fat diet group(HD group,n=50),fed withnormal chow and high fat diet respectively.12weeks later,40obese rats were randomlydivided into three subgroups:obesity model group(OB group,n=10),aerobic exercisegroup(AE group，n=10)，dietary control group（DC group，n=10) and metformin-treatedgroup (Met group,n=10).The rats in each intervention group were continue to feed thehigh-fat diet.The AE group take60minutes’ unload swimming6times per week,andother group did not have excise training.The amount of food intake every day of rats inDC group is calculated as70%of OB group.The Met group were lavaged with the samevolume but different concentrations(200mg/kg*d) of metformin solution.After sixweeks at the end of the experiment, blood samples were collected to determinemetabolic indexes. Adipose tissues of peri-kidney and peri-epididymis were dissectedand weighed.Lipid accumulation in skeletal muscle was analyzed by the lipid-specificOil Red O staining. Frozen sections of skeletal muscle stained withimmunofluorescence and western blot were evaluated to detect FAT/CD36expression.Results：（1）After18weeks of high-fat diet，BW,FBG,FINS,TG,TC and FFA levels of eachgroup in obesity model were higher than those in NC group with statistical significance（P <0.05),as well as metabolic indexes,the triglyceride levels and FAT/CD36expression levels in skeletal muscle tissue（P <0.05).（2）After6weeks intervention, the levels of FBG, FINS,FFA,HOMA-IR,TC in DCgroup decreased significantly compare to OB group(P <0.05); the levels of FBG,FINS,FFA,HOMA-IR,TG in AE group and Met group were down-regulated comparedto those in OB group (P <0.05);there were significant decreases in the levels ofFBG,FFA,HOMA-IR,TC,TG in Met group(P <0.05).（3）Both aerobic exercise and metformin treatment could reduce plasma TG、FFA level（P <0.05)，inhibit lipid accumulation in the abdominal cavity（P <0.05),decreasetriglyceride level in skeletal muscle tissue(P <0.05),so that release the insulinresistance in skeletal muscle.Although dietary control did not have a remarkable effecton the TG，FFA level and the lipid mass index（P>0.05)in obese rats,it could lower theplasma TC leve（lP <0.05)，and decrease triglyceride level in skeletal muscle tissue(P <0.05).（4）High-fat diet could induce increasing FAT/CD36expression levels in skeletalmuscle tissue(P <0.05),dietary control,aerobic exercise and metformin treatment coulddown-regulate the expression of FAT/CD36(P <0.05).（5）Correlation analysis: TG level in skeletal muscle tissue was possitively correlatedwith HOMA-IR index(r＝0.67, P <0.01) and the expression of FAT/CD36in highfat-diet rats(r＝0.69, P <0.01).Conclusion:1.This study successfully established nutrition obesity model in rats by feeding high fatdiet,and we found that the effect of lipotoxcity mainly cause glucose and lipidmetabolism disorder,excessive lipid accumulation in abdominal cavity and TG depositin skeletal muscle.2.Dietary control,aerobic exercise and metformin can improve the disorders of glucoseand lipid metabolism to some extent,inhibit lipid accumulation in the abdominalcavity,and down-regulate the expression of FAT/CD36.3.There was significant association between TG deposit and HOMA-IR,expression ofFAT/CD36，which hint that the accumulation of TG in muscle maybe participate insulinresistance in skeletal muscle;...