Wang Tian-Yuan, Wang Xiao-Hui
School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2020 Jul;36(4):312-317. doi: 10.12047/j.cjap.5945.2020.067.
To investigate the improved effects of 4-week aerobic exercise on blood glucose and lipid of diabetes mellitus (DM) rats and its association with peroxisome proliferators-activated receptor (PPAR)α signaling and PPARγ.
Six-week old male SD rats were fed with 8-week high-fat diet following a single intraperitoneal injection of streptozotocin to establish DM models rats. Except control group rats (fed with ordinary diet), DM model rats were randomly divided into DM group, trained DM group (TDM), TDM plus PPARγ agonist pioglitazone group (TDP), and TDM plus PPARγ inhibitor GW9662 group (TDG), 8 rats in each group. TDM, TDP and TDG rats were undertaken a medium-intensity incremental treadmill training for 4 weeks, once a day and 6 days a week (1 week: 15 m/min speed lasting for 30 min; 2 week: 15 m /min for 60 min; 3 week: 20 m/min for 60 min; 4 week: 20 m/min for 90 min). All the rats were fed with ordinary diet during 4-week exercise. The rats were anesthetized and blood samples were collected at 36 h after the last exercise, and liver and gastrocnemius were collected after the rats were sacrificed. Fasting blood glucose and blood lipid were detected (blood glucose, insulin and TC, TG, HDL and LDL). The protein levels of PPARα, adenosine monophosphate (AMP)-activated protein kinase (AMPK) and carnitine palmitoyl transferase 1 (CPT1) in the liver and gastrocnemius of the rats were measured by Western blot.
①Compared with control rats, the serum levels of TC, TG, LDL, and FBG (>11.1 mmol/L) in DM rats were significantly increased, indicated the successful establishment of DM rats. ②Compared with DM rats, accompanied with the improvements of fasting blood glucose and blood lipid, the protein levels of PPARα, AMPK and CPT1 were significantly increased in the liver and gastrocnemius of TDM rats. ③Compared with TDM rats, no significant changes were found in TDG rats including the protein levels of PPARα and CPT1 (liver and gastrocnemius) as well as AMPK (liver), except for a decrease of AMPK in gastrocnemius; while the protein levels of PPARα, AMPK and CPT1 were all increased in the liver and gastrocnemius of TDP rats.
Aerobic exercise-induced improvements of blood glucose and blood lipid was related to the up-regulation of AMPK-PPARα-CPT1 signaling pathway in the liver and muscle of DM rats. The exercise-induced enhancement of PPARα in DM rats was unrelated to PPARγ, but PPARγ activation could further increase the protein levels of AMPK-PPARα-CPT1 in TDM rats.
探讨4周有氧运动对糖尿病(DM)大鼠血糖和血脂的改善作用及其与过氧化物酶体增殖物激活受体(PPAR)α信号通路和PPARγ的关系。
6周龄雄性SD大鼠单次腹腔注射链脲佐菌素后,给予8周高脂饮食以建立DM模型大鼠。除对照组大鼠(给予普通饮食)外,将DM模型大鼠随机分为DM组、运动训练DM组(TDM)、TDM加PPARγ激动剂吡格列酮组(TDP)和TDM加PPARγ抑制剂GW9662组(TDG),每组8只。TDM、TDP和TDG组大鼠进行中等强度递增式跑步机训练4周,每天1次,每周6天(第1周:速度15 m/min,持续30 min;第2周:15 m/min,持续60 min;第3周:20 m/min,持续60 min;第4周:20 m/min,持续90 min)。在4周运动期间,所有大鼠均给予普通饮食。最后一次运动后36 h将大鼠麻醉并采集血样,处死大鼠后采集肝脏和腓肠肌。检测空腹血糖和血脂(血糖、胰岛素以及总胆固醇、甘油三酯、高密度脂蛋白和低密度脂蛋白)。采用蛋白质免疫印迹法检测大鼠肝脏和腓肠肌中PPARα、腺苷单磷酸(AMP)激活的蛋白激酶(AMPK)和肉碱棕榈酰转移酶1(CPT1)的蛋白水平。
①与对照大鼠相比,DM大鼠血清总胆固醇、甘油三酯、低密度脂蛋白和空腹血糖(>11.1 mmol/L)水平显著升高,表明DM大鼠模型建立成功。②与DM大鼠相比,TDM大鼠肝脏和腓肠肌中PPARα、AMPK和CPT1蛋白水平显著升高,同时空腹血糖和血脂得到改善。③与TDM大鼠相比,TDG大鼠肝脏和腓肠肌中PPARα和CPT1蛋白水平以及肝脏中AMPK蛋白水平无显著变化,腓肠肌中AMPK蛋白水平降低;而TDP大鼠肝脏和腓肠肌中PPARα、AMPK和CPT1蛋白水平均升高。
有氧运动诱导的血糖和血脂改善与DM大鼠肝脏和肌肉中AMPK-PPARα-CPT1信号通路的上调有关。运动诱导的DM大鼠PPARα增强与PPARγ无关,但PPARγ激活可进一步提高TDM大鼠中AMPK-PPARα-CPT1的蛋白水平。