有氧运动通过降低chemerin改善肥胖、糖尿病和动脉粥样硬化大鼠血糖、血脂及其机制的研究  

Aerobic exercise improves blood lipid and blood glucose of obese,diabetic and atherosclerotic rats by reducing chemerin

作　　者：林小晶 付绍婷 杨宏芳 王一兵 王晓慧 LIN Xiaojing;FU Shaoting;YANG Hongfang(School of Exercise and Health,Shanghai University of Sport,Shanghai,200438)

机构地区：[1]上海体育大学运动健康学院,上海市200438 [2]上海师范大学体育学院

出　　处：《中国康复医学杂志》2024年第11期1561-1571,共11页Chinese Journal of Rehabilitation Medicine

基　　金：国家自然科学基金项目(31872801);上海市人类运动能力开发与保障重点实验室(上海体育大学)(11DZ2261100)。

摘　　要：目的:利用外源chemerin证实chemerin在调控糖脂代谢中的作用并进一步研究其机制是否与外周代谢组织(肝、肌肉和脂肪)的过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptor γ, PPARγ)介导的糖脂代谢关键酶或蛋白包括脂蛋白甘油三酯酶(adipose triglyceride lipase,ATGL)、脂蛋白酯酶(lipoprotein lipase,LPL)和葡萄糖转运子4(glucose transporter 4,GLUT4)有关。方法:(1)动物实验:共纳入130只雄性6周龄SD大鼠。将大鼠随机分为正常对照组(Con,n=17)和建模组[采用8周高脂饲料、8周高脂饲料联合腹腔注射维生素D或小剂量链脲佐菌素分别建立肥胖(OB)、动脉粥样硬化(AS)和糖尿病(DM)的模型大鼠]。建模成功的各模型组大鼠再随机分为对照组[AS(n=8)、OB(n=8)和DM(n=10)]和运动组[EAS(n=8)、EOB(n=8)和EDM(n=10)]。各运动组大鼠进行为期4周中等强度的跑台运动,每周运动6天。检测各组大鼠的血清chemerin水平(ELISA),肝、腓肠肌、肾周脂肪的chemerin、CMKLR1、PPARγ、ATGL、LPL和GLUT4蛋白水平(Western Blot)。为证实PPARγ的介导作用,以DM大鼠为例,将DM大鼠随机分为4组:DM(n=10)、EDM(n=10)、EDM+PPARγ激动剂吡格列酮组(EDP,n=10)和EDM+PPARγ抑制剂GW9662组(EDG,n=10),检测ATGL、LPL和GLUT4蛋白水平。(2)细胞实验:为证实chemerin对PPARγ等蛋白的调控作用,用外源chemerin(200ng/ml)孵育3T3-L1细胞,48h后收集细胞检测PPARγ、ATGL、LPL和GLUT4蛋白水平。结果:(1)4周有氧运动改善AS、OB和DM大鼠血糖血脂的同时,其血清chemerin水平、组织(肝、腓肠肌和脂肪)的chemerin和CMKLR1水平均显著降低,而PPARγ、ATGL、LPL(肝、腓肠肌和脂肪)和GLUT4(骨骼肌)的蛋白水平显著升高。(2)在DM大鼠,PPARγ抑制剂GW9662显著降低、PPARγ激动剂吡格列酮显著增强有氧运动对ATGL、LPL和GLUT4的增加作用。(3)外源chemerin处理3T3-L1细胞后,PPARγ、ATGL、LPL和GLUT4蛋白表达水平显著降低。结论:Objective:To confirm the role of decreased chemerin on aerobic exercise-induced improvement of glucose and lipid metabolism using exogenous chemerin in obese,diabetic and atherosclerotic rats,and to explore whether the mechanisms is related to the key enzymes or proteins of glucose and lipid metabolism mediated by peroxisome proliferator-activated receptorγ(PPARγ)in the peripheral metabolic organs(liver,muscle and fat),including lipoprotein triglyceride lipase(ATGL)and lipoprotein lipase(LPL)and glucose transporter 4(GLUT4).Method:①Animal experiments:Total of 130 male rats aged 6 weeks were included in this study.In addition to the normal control(Con,n=17)rats,the model rats with obesity(OB),atherosclerosis(AS)and diabetes mellitus(DM)were established by 8-week high-fat diet,8-week high-fat diet combined with intraperitoneal injection of Vitamin D3 or of low dose of streptozotocin,respectively.All the successfully established model rats were randomly divided into:the control[AS(n=8),OB(n=8)and DM(n=10)and the exercise EAS(n=8),EOB(n=8)and EDM(n=10)]rats.All exercise groups were participated in the 4-week moderate-intensity treadmill running exercise with gradually increased load,six days per week and one time per day.Serum chemerin were detected by ELISA.Protein levels of chemerin,CMKLR1,PPARγ,ATGL,LPL and GLUT4 in tissues(liver,gastrocnemius and perirenal fat)were detected by Western blot.In order to confirm the mediation role of PPARγ,diabetic rats were randomly divided into 4 groups:DM(n=10),EDM(n=10),EDM plus PPARγagonist pioglitazone(EDP,n=10)and EDM plus PPARγantagonist GW9662(EDG,n=10),and the protein levels of ATGL,LPL and GLUT4 were detected.②Cell experiments:3T3-L1 cells were treated with exogenous chemerin(200 ng/ml)for 48 h,then the cells were collected to detect the protein levels of PPARγ,ATGL,LPL and GLUT4.Result:①The serum chemerin and the protein levels of chemerin and CMKLR1 in tissues(liver,gastrocnemius and perirenal fat)of EAS,EOB and EDM groups rats were significantly decreased

关 键 词：有氧运动 CHEMERIN 动脉粥样硬化 2型糖尿病 糖脂代谢 

分 类 号：Q45[生物学—生理学] R493[医药卫生—康复医学]