有氧运动调控琥珀酸盐/SUCNR1信号级联改善肥胖相关胰岛素抵抗  

Aerobic exercise ameliorates insulin resistance in obese mice via regulating succinate/SUCNR1 signaling cascade

作　　者：汪洋 毋江波[2] 蔺海旗[3] WANG Yang;WU Jiang-bo;LIN Hai-qi(不详;Sports Department of Tianjin Cheng Jian University,Tianjin 300384,China)

机构地区：[1]天津城建大学体育部,天津300384 [2]天津体育学院 [3]华南理工大学体育学院

出　　处：《现代预防医学》2022年第13期2441-2446,2464,共7页Modern Preventive Medicine

基　　金：天津市自然科学基金(18JCQNJC12400)。

摘　　要：目的探讨有氧跑台运动调控肠道琥珀酸盐/SUCNR1信号改善肥胖相关胰岛素抵抗的作用机制。方法8周龄雄性C57BL/6和SUCNR1缺失小鼠随机分为对照组、高脂模型组和高脂模型+运动组。对照组和高脂组分别喂食普通膳食和高脂饲料,运动组为连续8周的跑台运动:15米/分,1 h/天,5天/周。结合16s rRNA测序和质谱分析肠道菌群及肠道琥珀酸盐含量;采用血糖检测仪检测血糖和酶偶联反应检测胰岛素、葡萄糖6磷酸(G6P)和糖原(Glycogen)含量;WB检测肠道葡萄糖6磷酸酶(G6Pase)和磷酸烯醇丙酮酸羧激酶(PEPCK)的表达。结果高脂处理下调肠道琥珀酸盐(99.08±10.99 vs 14.65±4.462),抑制肠道SUCNR1(下调66%)、G6Pase(下调40%)和PEPCK(下调45%)蛋白表达,促进肝脏G6P表达(1.77倍)和糖原储存(1.68倍),提示肠道糖异生受到抑制,肝脏糖异生得到提升,诱导胰岛素抵抗;有氧运动干预逆转上述变化,提高胰岛素敏感性。SUCNR1缺失小鼠阻断了有氧运动对肥胖相关胰岛素抵抗的改善作用。结论有氧运动促进肠道琥珀酸盐,琥珀酸盐/SUCNR1信号通过促进肠道糖异生,降低肝脏糖异生,从而改善肥胖小鼠胰岛素抵抗。Objective To explore the regulatory mechanism underlying aerobic exercise-mediated the improvement of obesity-related insulin resistance through regulating succinate/SUCNR1 signaling cascade.Methods Eight-week old male c57 BL/6 and SUCNR1 deletion mice were enrolled in this study and randomly divided into control group,high-fat model group and high-fat+aerobic exercise intervention group.Control mice were subjected with regular chow,and a high-fat model was established by subjecting with high-fat diet.Aerobic exercise intervention was performed at 15 m per minute,1 h/day,5 days/week,for consecutive 8 weeks.Gut microbiota and intestinal succinate were detected by 16 s rRNA sequencing and Mass Spectrometry,respectively.Fasting serum glucose was monitored by portable brood glucose,and serum insulin,liver G6 P content and liver glycogen content were measured by ELISA assay.Protein levels of glucose-6-phosphatase(G6 Pase)and phosphoenolpyruvate carboxykinase(PEPCK)were determined by WB assay.Results High-fat diet reduced intestinal succinate contents,inhibiting protein levels of enteric SUCNR1,G6 Pase and PEPCK,and promoted liver G6 P level and liver glycogen contents,subsequently leading to the decline in intestinal gluconeogenesis and the increase in liver gluconeogenesis,which resulted in insulin resistance.However,aerobic exercise rescued the changes induced by high-fat diet,leading to the increase of insulin sensitivity.The protective role of aerobic exercise on obesity-related insulin resistance was abolished in high-fat-challenged SUCNR1 mice.Conclusion Aerobic exercise upregulated the production of intestinal succinate,and ameliorated insulin resistance through promoting intestinal gluconeogenesis and inhibiting liver gluconeogenesis via SUCNR1 signaling in obese mice.

关 键 词：有氧运动 胰岛素抵抗 琥珀酸盐 糖异生 琥珀酸盐受体 

分 类 号：R165[医药卫生—公共卫生与预防医学] G804.7[文化科学—运动人体科学]