高强度间歇训练对2型糖尿病小鼠内脏脂肪线粒体自噬及棕色化影响的研究  

Effects of high intensity interval training on mitophagy and browning of white fat in type 2 diabetic rats

作　　者：赖明慧 郭一帆 于小明[2] 蒋黎明[2] 肖卫华[1] LAI Minghui;GUO Yifan;YU Xiaoming(School of Kinesiology,Shanghai University of Sport,Shanghai 200438,China)

机构地区：[1]上海体育学院运动科学院,200438 [2]上海中医药大学附属第七人民医院康复医学中心

出　　处：《中国糖尿病杂志》2023年第6期443-450,共8页Chinese Journal of Diabetes

基　　金：上海市科技计划项目(23010504200);上海市曙光计划项目(20SG50);上海市人才发展资金(2020125);上海体育学院运动健身科技省部共建教育部重点实验室(2022KF001);上海体育学院上海市人类运动能力开发与保障重点实验室(11DZ2261100)。

摘　　要：目的观察8周高强度间歇训练(HIIT)对T2DM小鼠内脏脂肪线粒体自噬和棕色化的影响,分析线粒体自噬与棕色化的相关性。方法30只C57BL/6J雄性小鼠分为正常对照(Con)组、DM安静组(SED组)和DM运动组(HIIT组),每组各10只。各组采取相应干预,比较小鼠体重、附睾脂肪重量,HE染色观察脂肪细胞形态,免疫组化观察解偶联蛋白1(UCP1)蛋白表达,RT-PCR检测Ins信号通路相关因子基因[磷脂酰肌醇激酶(PI3K)、蛋白激酶B(AKT)、IRS-1、GluT4]、棕色化基因[UCP1、PR域锌指蛋白16(Prdm16)、Ⅱ型脱碘酶(DIO-2)、过氧化物酶体增殖物激动受体(PPARα)、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC1α)、沉默信息调节因子1(Sirt1)、核呼吸因子1(Nrf-1)、细胞死亡诱导DFFA样效应蛋白A(Cidea)]、线粒体自噬相关基因[自噬基因(Beclin)、E3泛素连接酶(Parkin)、自噬相关基因(Atg7)、选择性自噬接头蛋白(P62)]表达。结果与SED组比较,HIIT组脂肪重量、体脂率、脂肪细胞面积降低(P<0.01),PI3K、AKT、IRS-1、GluT4、UCP1、Prdm16、PPARα、DIO-2、PGC1α、Sirt1、Nrf-1、Cidea、P62 mRNA表达升高(P<0.05或P<0.01),Beclin、Parkin、Atg7 mRNA表达降低(P<0.05或P<0.01)。Pearson相关分析显示,Parkin与UCP1mRNA表达呈负相关(P=0.012),P62与UCP1 mRNA表达呈正相关(P=0.0003)。结论8周HIIT可促进T2DM小鼠内脏脂肪棕色化,此过程可能与线粒体自噬抑制相关。Objective To investigate the effect of 8-week high-intensity intermittent trainingon mitophagy and browning in visceral adipose tissue of type 2 diabetes mellitus(T2DM)rats,and analyze the correlation between mitophagy and browning marker genes.Methods30 C57BL/6J male mice were divided into control(Con)group,diabetes sedentary(SED)group and high-intensity intermittent training(HIIT)group.After the above intervention,we compared the body mass and epididymis mass of rats among the groups.HE staining was used to evaluate the morphology of adipocytes.The expression of UCP1 was tested by immunohistochemical staining.RT-PCR was used to investigate insulin signaling pathway related factor genes[phosphatidylinositol kinase(PI3K),protein kinase B(AKT),IRS-1,GluT4],browning gene[UCP1,PR domain zinc finger protein 16(Prdm16),typeⅡdeiodinase(DIO-2),peroxisome proliferatoractivated receptor(PPARα),peroxisome proliferator activated receptorγco-activation factor 1α(PGC1α),silent information regulatory factor 1(Sirt1),nuclear respiratory factor 1(Nrf-1),cell death induction DFFA-like effector protein A(Cidea)],mitochondrial autophagy-related genes[autophagy genes(Beclin),E3ubiquitin ligase(Parkin),autophagy related genes(Atg7),and selective autophagy junction protein(P62)].ResultsCompared with SED group,fat weight,body fat rate,adipocyte area decreased(P<0.01),PI3K,AKT,IRS-1,GluT4,UCP1,Prdm16,PPARα、DIO-2,PGC1α,Sirt1,Nrf-1,Cidea,P62 mRNA expression increased(P<0.05 or P<0.01),while Beclin,Parkin and Atg7 mRNA expression decreased in HIIT group(P<0.05 or P<0.01).Pearson correlation analysis showed that Parkin was negatively correlated with UCP1 mRNA expression(P=0.012),while P62 was positively correlated with UCP1 mRNA expression(P=0.0003).ConclusionEight-week HIIT can promote visceral fat browning in T2DM rats,which is related to the inhibition of mitophagy.

关 键 词：糖尿病 2型 高强度间歇训练 脂肪组织棕色化 线粒体自噬 

分 类 号：R587.1[医药卫生—内分泌]