| ObjectivesIt is widely accepted that the impaired glucose and lipid metabolism contributes largely to the development of obesity?OB?and its related diseases including diabetes mellitus?DM?and atherosclerosis?AS?.It is well known that regular aerobic exercise can improve and retrieve the disorders of glucose and lipid metabolism,while the underlying mechanism still remains largely unknown.Androgen,as a steroid hormone,mainly exerts its biologic functions through binding to androgen receptor?AR?.Latest evidences from basic and clinical researches indicate that androgen and AR exert important roles in regulating glucose and lipid metabolism apart from its essential functions in promoting and maintaining male primary and secondary sexual characteristics,skeletal muscle mass and force as well as bone mineral density and mass.Although the roles of androgen/AR signal pathway in exercise-induced increases of muscle mass and exercise performance have been well demonstrated,there is a few reports about the effects of androgen/AR in exercise-induced improvement of glucose and lipid metabolism in obesity and obesity related diseases,let alone the underlying mechanisms.It has been reported that androgen/AR modulated the level of phosphoenolpyruvate carboxy kinase?PEPCK?,which is a key enzyme to raise blood glucose by promoting gluconeogenesis.Therefore,the purpose of this study is to investigate the roles of androgen/AR in aerobic exercise-induced improvement of glucose and lipid metabolism in OB,DM and AS rats and its possible mechanism,which is beneficial to understand the mechanism of prevention and treatment of exercise on obesity and obesity related diseases.MethodsOne hundred and thirty six Sprague-Dawley?SD?male rats aged six weeks were randomly divided into normal diet group?n=26?and high fat diet group.OB,DM and AS model rats were established via 8-week of high fat diet,high fat diet plus intraperitoneal injection of small dose streptozotocin?30 mg/kg of body weight?or plus Vitamin D3 injection,respectively.Then,the successfully established model rats were divided into OB,OB plus exercise?EOB?,AS,AS plus exercise?EAS?,8 rats for each group;and DM,DM plus exercise?EDM?,10 rats for each group.In addition,26 rats fed with normal diet were divided to 3 groups:control group?CON,n=10?,Flutamide embed group?a AR antagonist Flutamide sustained-release pellet was implanted subcutaneously by making a tiny incision in the neck skin of rat to inhibit AR??n=8?and sham group?only taken the same surgery without embed pellet??n=8?.EOB,EDM and EAS rats were undertaken 4-week moderate intensity exercise with progressively increasing load on a treadmill running?1st week:running speed of15 m/min for 30 min;2nd week:15 m/min,60 min;3rd week:20 m/min,60 min and4th week:20 m/min,90 min?.In each week,the body weight and food intake as well as fasting blood glucose?FBG?of the rats were measured.At 36 hour after the last session of exercise,the rats were anaesthetized and sacrificed,then the serum,liver,gastrocnemius and perirenal fat samples were collected.Blood lipid indexes including TC,TG,LDL and HDL,and blood glucose fasting serum insulin?FINS?were detected,and insulin resistance reflected by HOMA-IR were calculated according to FBG and FINS.Serum testosterone and the protein levels of AR and PEPCK in liver,gastrocnemius and adipose were determined by ELISA and Western blot,respectively.Results1.Successful establishment of OB,DM and AS modelsThe average body weight of OB rats increased beyond 20%?647±35.68 vs 523±33.89 g?than that of CON rats,and FBG of DM rats were 15.50±3.76 mmol/L over the criteria of DM?11.1 mmol/L?,and AS rats appeared the specific lesion including AS plaque,proliferation of smooth muscle cell and thicker blood vessel,which indicated the successful establishment of OB,DM and AS models.2.Improvement of blood glucose and lipid as well as alleviation of symptoms by4-week of aerobic exercise in OB,DM and AS ratsCompared with CON rats,disorders of blood glucose and lipid including the enhanced HOMA-IR,serum TC,TG,LDL were observed in OB,DM and AS rats?increased FBG and decreased HDL also showed in DM rats?,which were all improved by 4-week of aerobic exercise,reflected by obvious decreases in TG,LDL and HOMA-IR in EOB rats,LDL in EAS rats,and TC,TG,LDL,HOMA-IR in EDM rats.In addition to the improvement of blood glucose and lipid,the disease symptoms were also ameliorated dramatically,including the reduction of body weight in EOB rats at the third week of exercise?from 641.88±34.77 g to 593.25±39.93 g?,the attenuations of FBG levels in DM rats and the mitigation of pathological lesions in EAS rats.3.Correlation analysis of serum testosterone with blood glucose and lipid,and effect of 4-week aerobic exercise on serum testosteroneCompared with CON rats,noticeable decreases of serum testosterone were observed in OB,DM and AS rats with no significant difference between groups.Four weeks of aerobic exercise greatly increased the levels of serum testosterone in EOB and EAS rats while no changes in EDM rats.Pearson correlation analysis indicated a significant negative correlation of testosterone with TG or LDL.Considering a big individual difference of serum testosterone in ordinary males,the rats with extreme testosterone values were carefully observed the levels of blood glucose and lipid,and we found that much higher levels of TG,TC,LDL and FBG in the rats with extremely lower testosterone level,and relative lower TG,TC,LDL and FBG in extremely higher testosterone rats.4.Effects of 4-week aerobic exercise on AR protein levels in the liver,gastrocnemius and adipose tissue of OB,DM and AS ratsCompared with CON group,the protein levels of AR in OB?liver,gastrocnemius?,DM?liver?and AS?gastrocnemius?rats were significantly decreased,while no noticeable difference of AR was found in the adipose tissue of OB and AS rats.Four weeks of aerobic exercise greatly increased the AR protein levels of EOB?gastrocnemius,adipose tissue?,EDM?liver?and EAS?liver,gastrocnemius?rats,while no change of AR in the liver of EOB and gastrocnemius of EDM rats.5.Effects of AR antagonist Flutamide on the blood glucose and lipid of normal rats.For verification of the roles of AR in blood glucose and lipid,AR antagonist Flutamide sustain-release pellet was implanted subcutaneous in the neck of rats.Results showed significant increases in the levels of TC,TG and LDL and only a trend of increases in FINS and FBG,compared with sham group.6.Effects of 4-week aerobic exercise on the protein level of PEPCK,a crucial enzyme of gluconeogenesis,in the liver and gastrocnemius of OB and DM ratsCompared with CON group,significant increase in the protein level of PEPCK were observed in the livers of OB rats and in the liver and gastrocnemius of DM rats,which were significantly decreased by 4-week aerobic exercise.It has been reported that PEPCK was regulated by peroxisome proliferator activated receptor??PPAR??,and PPAR?was modulated by AR.In addition,our previous studies has demonstrated that 4-week aerobic exercise-induced improvement of blood glucose and lipid in the OB and DM rats was likely to be related to the activation of PPAR?and its target genes:glucose and lipid metabolism crucial enzymes such as adipose triglyceride lipase?ATGL?and lipoprotein lipase?LPL?.Conclusions1.Decreases of androgen and AR were associated with the impaired blood glucose and blood lipid in OB,DM and AS rats.2.Increases of androgen/AR by 4-week exercise were related to the improvements of blood glucose and blood lipid in OB,DM and AS rats,and the roles of androgen/AR might be mediated by regulating glycolipid metabolism key enzymes like PEPCK. |
PDF Full Text Request