Mechanisms Of Improved Glycolipid Metabolism Through Aerobic Exercise In Ob/ob Mice

ObjectAs a new inflammatory cytokine,chemerin plays an important role in the regulation of glycolipid metabolism.The levels of chemerin in serum and liver,fat tissue are significantly increased under obesity and obesity-related disease conditions such as fatty liver,diabetes and atherosclerosis.Lifestyle changes(exercise and dietary control)or bariatric surgery can significantly reduce chemerin levels in serum and tissues while improving glycose and lipid metabolism.We have previously confirmed that aerobic exercise could reduce body fat and improve the glycolipid metabolism in obese and diabetic rats,which may be achieved by increasing the expression of key enzymes involved in fat metabolism—lipoprotein lipase(LPL)and adipose triglyceride(ATGL).Due to the lack of rat commercial chemerin recombination protein,the effect of chemerin on glucose and lipid metabolism,and whether the role of chemerin in the regulation of glycolipid metabolism was mediated by LPL and ATGL have not been confirmed.We aimed to investigate whether 6-week aerobic exercise could reduce ob/ob mice chemerin levels in liver,skeletal muscles and adipose tissues,and whether this effect is related to LPL and ATGL,providing foundation for verifying the role of chemerin in improving glucose and lipid metabolism-induced by aerobic exercise and whether this effect is mediated by ATGL and LPL.In addition to chemerin,IGF-1 plays a significant role in improving glycolipid metabolism disorder in obesity and obesity-related diseases,and glycolipid metabolism disorder improvements by exercise,at least partly,were achieved by increasing serum IGF-1 levels and activities.It should be mentioned that there is negative correlation between IGF-1 and leptin level in obesity and obesity-related diseases.In ob/ob mice,leptin gene mutation leads to leptin deficiency,resulting in obesity and glycolipid metabolism disorder in mice.Hence,in the second part of this study,we aimed to investigate the level of serum and liver IGF-1 and IGF-1R in ob/ob mice,and the effect of 6-week aerobic exercise on IGF-1 and IGF-1R levels.,thus exploring the role of the IGF-1 signal pathway in improving glycolipid metabolism-induced by exercise in ob/ob mice lacking leptin.MethodsThe 6-week old mice were divided into ob/ob group(ob/ob,n=5)and ob/ob exercise group(Tob,n=5).And the C57 were chose as control(Con,n=5).During the experiment,the mice were fed with normal diet.Tob group participated in 6-week aerobic exercise on treadmill with gradually intensity(from 12m/min for the first 3 weeks to 14m/min for the last 3 weeks)and duration(1 hour per day),once a day and 5 days per week.The body weight and fasting blood glucose were examined weekly.Blood and tissue samples were collected 36 hours after the last exercise finished.Lipid metabolism index(including total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL)and high-density lipoprotein cholesterol(HDL)),fasting insulin level and fasting IGF-1 levels(ELISA)were detected,And the protein levels of chemerin,GLUT4,LPL,ATGL,IGF-1 and IGF-1R in liver,gastrocnemius and perirenal adipose were detected by Western Blot.The experiment data would be analyzed by SPSS20.0 Statistical software.Ob/ob mice’s body weight would be analyzed by the variance of repeated measures,and the other index would be analyzed by the single factor analysis of variance.Results1.6-week aerobic exercises could improve the fatty liver and the glycolipid metabolism in ob/ob mice.In ob/ob mice,the liver index was significantly increased and liver presenting big,yellow and oily changes suggesting that fatty liver occurred.However,liver indexes were significantly reduced by 6-week aerobic exercise and the big,yellow and oily changes were alleviated.The glucose and lipid metabolism disorder occurred in ob/ob mice.And after 6-week aerobic exercise intervention,serum LDL,FINS and HOMA-IR level were reduced significantly.2.6-week aerobic exercise significantly reduce the chemerin protein level in livers and perirenal adipose in ob/ob mice.Comparing with control group,the chemerin protein levels in livers and perirenal fat in ob/ob mice were increased significantly.And after 6-week aerobic exercise intervention,the chemerin protein level in livers and perirenal adipose of ob/ob mice were reduced significantly.3.6-week aerobic exercise could significantly increase the LPL protein level in livers and the ATGL protein level in the perirenal adipose of ob/ob mice.Comparing with control group,LPL protein level in livers and ATGL protein level in perirenal adipose of ob/ob mice were decreased significantly.And after 6-week aerobic exercise intervention,LPL protein levels in livers and ATGL levels in perirenal adipose of ob/ob mice were increased significantly.4.6-week aerobic exercise could significantly reduce the serum and gastrocnemius IGF-1 level,and gastrocnemius IGF-1R protein level in ob/ob mice.Comparing with control group,serum IGF-1 levels and gastrocnemius IGF-1R protein levels in ob/ob mice were significantly increased.And after the 6-week aerobic exercise,serum IGF-1 levels has a significant reduction,and IGF-1 and IGF-1R protein level in gastrocnemius were reduced significantly.5.6-week aerobic exercise could significantly reduce the gastrocnemius GLUT4 protein level.In ob/ob mice,gastrocnemius GLUT4 protein levels were increased significantly comparing with control,and were reduced significantly after 6-week aerobic exercise intervention.Conclusions1.6-week aerobic exercise significantly improves ob/ob mice glycolipid metabolism disorder and fatty liver,which may be related to the down-regulation of chemerin protein levels induced by exercise,up-regulation of the key enzymes involved in glycolipid metabolism—liver LPL and the ATGL protein levels in perirenal adipose of ob/ob mice.However,whether the reduced chemerin is achieved by increasing LPL and ATGL to improve glycolipid metabolism remains to be confirmed.2.The serum and gastrocnemius IGF-1 levels in ob/ob mice were abnormal increased.However,6-week aerobic exercise could reduce serum and gastrocnemius IGF-1 levels and the gastrocnemius IGF-1R protein levels significantly,this may contribute to the improvement of glycolipid metabolism disorder and fatty liver in ob/ob mice induced by exercise.