| Object Chemerin,an adipokine and inflammatory cytokines,is closely related to the occurrence and severity of obesity and type 2 diabetes as well as the disorder of glucose and lipid metabolism.Disorder of glucose and lipid metabolism,especial insulin resistance plays an importance role on the occurrence and development of obesity and diabetes.Exercise can improve glucose and lipid metabolism,which contributed to the prevention and treatment of obesity and diabetes.Whether the improvement of glucose and lipid metabolism induced by exercise is associated with the change of chemerin in obesity and diabetes? The mechanisms by which exercise induced chemerin alteration and the modulated-chemerin improved glucose and lipid metabolism in obesity and diabetes are still unclear.One of the purposes of the study was to determine the effect of 4 weeks aerobic exercise on the levels of chemerin(serum,liver and gastrocnemius)and chemerin receptor CMKLR1(liver and gastrocnemius)in obesity and diabetes rats,and to detect the relationship between exercise-induced chemerin/CMKLR1 alterations and peroxisome proliferator activated receptor ?(PPAR?),a molecular linking glucose and lipid metabolism and inflammation.Another purpose of the research was to elucidate whether aerobic exercise-regulated chemerin/CMKLR1 alterations of diabetic rats were mediated by PPAR? using PPAR? agonist pioglitazone and antagonist GW9662;and whether the change of chemerin improved glucose and lipid and lipid metabolism of diabetes rats was associated with PPAR? target genes adipose triglyceride lipase(ATGL)and lipoprotein lipase(LPL).Methods One hundred and two male Sprague-Dawley(SD)rats were randomly divided into control group(Con,n=8)and high fat diet group.Control rats were fed with normal diet,while high fat diet rats ingested 8-week high fat diet.Then establishment of obesity model rats and type 2 diabetes model rats.the high fat diet group were intraperitoneal injected streptozotocin at the dose of 30 mg/kg body weight to establish diabetes model rats.The obesity model group and were randomly divided into obesity group(OB)and exercised obesity group(EOB).The 40 of diabetes model rats were successfully obtained.To determine whether the effect of exercise on chemerin and CMKLR1 of diabetes rats is mediated by PPAR?,40 of diabetes model rats were randomly divided into 4 groups of 10 rats each: diabetes group(DM),exercised diabetes group(EDM),exercised diabetes plus PPAR? agonist pioglitazone group(EDP),and exercised diabetes plus PPAR? antagonist GW9662 group(EDG).During the 4-week aerobic exercise and PPAR? agonist/antagonist interventions,all the rats were fed with normal diet.The rats in EOB,EDM,EDG and EDP groups participated in a 4-week moderate-intensity aerobic exercise on a treadmill with gradually increasing intensity(from 15 m/min in the 1st-2nd weeks to 20 m/min in the 3rd-4th weeks)and duration(from 30 min in the first week,60 min in the 2st-3rd weeks to 90 min in the fourth week),once a day and 6 days/week.Before and after 4-week experiments,lipid metabolism index of the rats including triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL)and low-density lipoprotein cholesterol(LDL)were detected by Nanjing Jiancheng Bioengineering Institute;and glucose metabolism index of the rats such as FBG and fasting insulin(FINS)were measured by glucose meter and ELISA,respectively.Insulin resistance(HOMA-IR)was calculated using the formula: HOMA-IR=FBG(mmol/L)? FINS(mIU/m L)/ 22.5.In addition,serum level of chemerin was determined by ELISA.The m RNA and protein expressions of chemerin,CMKLR1,PPAR?,ATGL and LPL in livers and gastrocnemius were detected by real time PCR and Western blot,respectively.Results 1.Improvement of glucose and lipid metabolism in obesity and diabetes rats resulted from 4-week aerobic exercise.There were disorders of glucose and lipid metabolism in both OB and DM rats,with more severe disorder in DM rats.Four weeks aerobic exercise improved the glucose and lipid metabolism of OB and DM rats,representative of decreased levels of FINS,HOMA-IR,TG and LDL in OB rats and attenuated levels of FBG,FINS,HOMA-IR,TC,TG and LDL in DM rats.2.Decreases of chemerin in the serums,livers and gastrocnemius of diabetes rats while only in the livers of obesity rats induced by 4-week aerobic exercise.The levels of chemerin in serum,livers and gastrocnemius were significantly increased in OB and DM rats,with higher chemerin in DM rats.Four weeks aerobic exercise significantly decreased the levels of chemerin in the serums,livers and gastrocnemius of DM rats while only in the livers of OB rats.3.Reductions of CMKLR1 in the livers and gastrocnemius of obesity and diabetes rats induced by 4-week aerobic exercise.The levels of CMKLR1 were significantly increased in the livers and gastrocnemius of OB and DM rats,with higher CMKLR1 in DM rats.Four weeks of aerobic exercise significantly decreased the levels of CMKLR1 in the livers and gastrocnemius of OB and DM rats.4.Enhancements of PPAR? as well as ATGL and LPL(PPAR? target genes)in the livers and gastrocnemius of obesity and diabetes rats resulted from 4-week aerobic exercise.The protein levels of PPAR?,ATGL and LPL in gastrocnemius and ATGL in livers of DM rats were reduced,while only decreased LPL in gastrocnemius of OB rats were found.Four weeks aerobic exercise significantly increased the protein levels of PPAR?,ATGL and LPL in livers and gastrocnemius of OB and DM rats.5.Exercise-induced improvement of glucose and lipid metabolism in diabetes rats was mediated by PPAR?.The improvement of glucose and lipid metabolism induced by exercise was reversed by GW9662 and further improved by pioglitazone,which indicated that exercise-induced improvement of glucose and lipid metabolism in diabetes rats might be mediated via PPAR?,and exercise in combination with PPAR? agonist might be more effective than exercise alone in improving the glucose and lipid metabolism of diabetes rats.6.Exercise-induced down-regulations of chemerin and CMKLR1 in diabetic rats were mediated by PPAR?.For clarifying the role of PPAR? on exercise-induced decreases of chemerin and its receptor CMKLR1 in diabetes rats,PPAR? antagonist GW9662 and agonist pioglitazone were used at 30 min before exercise to inhibit and stimulate PPAR? signaling.The exercise-induced down-regulations of chemerin and CMKLR1 in the livers and gastrocnemius of diabets rats were reversed by GW9662,while no significant change of serum chemerin was found by GW9662.In addition,pioglitazone further strengthen the reductions of serum chemerin and protein levels of chemerin(livers)and CMKLR1(gastrocnemius)of diabetes rats.These results indicated that exercise-induced down-regulations of chemerin and CMKLR1 in diabetes rats might be mediated by PPAR?,and exercise in combination with PPAR? agonist might be more effective than exercise alone in decreasing chemerin and CMKLR1 levels in diabetes rats.7.Exercise-induced up-regulations of ATGL and LPL in the livers and gastrocnemius of diabetic rats were mediated by PPAR?.The increased expressions of ATGL and LPL in the livers and gastrocnemius of DM rats resulted from exercise were reversed by GW9662 except for LPL expression in the gastrocnemius and further enhanced by pioglitazone,which indicated that exercise-induced up-regulations of ATGL and LPL in diabetes rats might be mediated by PPAR?,and exercise in combination with PPAR? agonist might be more effective than exercise alone in up-regulating ATGL and LPL of diabetes rats.Conclusions 1.The levels of chemerin in the serums,livers and gastrocnemius and of CMKLR1 in the livers and gastrocnemius were significantly increased in obesity and diabetes rats,with higher levels in diabetes rats.2.Four weeks of aerobic exercise decreased the levels of chemerin(serums,livers and gastrocnemius)and CMKLR1(livers and gastrocnemius)in obesity and diabetes rats,which might be related to exercise-induced improvement of glucose and lipid metabolism in obesity and diabetes rats.3.Four weeks of aerobic exercise increased the levels of PPAR?,ATGL and LPL in livers and gastrocnemius of obesity and diabetes rats,which contributed to the improvement of glucose and lipid metabolism in obesity and diabetes rats.4.In diabetes rats,4-week aerobic exercise-induced decreases of chemerin and CMKLR1 were likely to be mediated by PPARg.5.In diabetes rats,4-week aerobic exercise-induced increases of ATGL and LPL(glucose and lipid metabolism related enzymes)were likely to be mediated by PPARg,thus improving glucose and lipid metabolism of diabetes rats.6.Aerobic exercise in combination with PPAR? agonist might be more effective than exercise alone in decreasing chemerin and CMKLR1,increasing ATGL and LPL and improving glucose and lipid metabolism of diabetes rats.7.Whether the reduced chemerin resulted from 4-week exercise was via the mediation of increased ATGL and LPL to achieving the improvement of glucose and lipid metabolism is worth of further study. |
PDF Full Text Request