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有氧运动抑制胰岛素抵抗小鼠肝脏糖异生及FNDC5/Irisin调控研究 被引量:3

Inhibition of Aerobic Exercise on Liver Gluconeogenesis in Insulin Resistant Mice and the Regulation of FNDC5/Irisin
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摘要 目的 探讨8周有氧运动对IR小鼠肝脏糖异生及FNDC5/Irisin/Akt/FoxO1/PEPCK/G6Pase信号的影响。方法 5周龄C57BL/6雄性小鼠随机分为对照组(Con组,n=16)和高脂膳食组(HFD组,n=34),干预12周建立IR模型。建模成功后,IR模型小鼠随机分为IR安静组(IR-Sed组,n=8)和IR运动组(IR-Ex组,n=8);Con组随机分为Con安静组(Con-Sed组,n=8)和Con运动组(Con-Ex组,n=8)。Con-Ex和IR-Ex组进行8周跑台运动(18 m/min,60 min/天,5 d/周)。12周建模后和末次运动后检测胰岛素敏感性,末次运动48 h后取血和肝脏进行相关检测。结果 与Con组相比,HFD组体质量、FINS、FPG、HOMA-IR和AUC_(BG)均升高(P<0.01),ISI、葡萄糖耐量和胰岛素耐量均下降(P<0.01)。与IR-Sed组相比,8周有氧运动后IR-Ex组体质量、FINS、FPG、HOMA-IR和AUC_(BG)均降低(P<0.01),ISI、葡萄糖耐量和胰岛素耐量均升高(P<0.01)。同时,与Con-Sed组相比,IR-Sed组肝细胞发生脂肪变性,TG和血清ALT、AST含量均增加(P<0.01),PAS染色稀薄并呈不均匀样,肝糖原含量下降(P<0.01),PEPCK、G6Pase和FoxO1含量均增加(P<0.05),FNDC5、Irisin、p-Akt和p-FoxO1水平均降低(P<0.05);与IR-Sed组相比,8周有氧运动后IR-Ex组肝细胞脂肪变性得到改善,TG和血清ALT、AST含量均下降(P<0.01),PAS染色相对饱满均匀,肝糖原含量增加(P<0.05),PEPCK和G6Pase表达下降(P<0.01),FNDC5、Irisin、p-Akt和p-FoxO1水平均增加(P<0.01)。结论 长期有氧运动干预有效抑制肝脏糖异生并改善IR,可能与FNDC5/Irisin促进肝脏组织中Akt蛋白激活,进而促进FoxO1磷酸化使其蛋白失活,抑制糖异生关键酶PEPCK和G6Pase表达并改善肝脏功能有关。 Objective To explore the effects of 8-week aerobic exercise on FNDC5/Irisin/Akt/FoxO1/PEPCK/G6 Pase pathway and liver gluconeogenesis in IR mice.Methods 5-week C57 BL/6 male mice were randomly divided into Control group(Con group,n=16) and high fat diet group(HFD group,n=34) to prepare insulin resistance(IR) model.After 12 weeks,IR mice were randomly divided into IR-Sedentary group(IR-Sed group,n=8) and IR-Exercise group(IR-Ex group,n=8);Control mice were randomly divided into Con-Sedentary group(Con-Sed group,n=8) and Con-Exercise group(Con-Ex group,n=8).In Con-Ex and IR-Ex group,8-week treadmill aerobic exercise(18 m/min,60 min/day,5 days/week) was performed.Insulin sensitivity was measured after 12 weeks of HFD and the last exercise.Blood and liver were taken for further detection after the last exercise.Results Compared with Con group,the weight,FINS,FPG,HOMA-IR and AUC_(BG) in HFD group were increased(P<0.01),and the ISI,glucose and insulin tolerance were decreased(P<0.01).After 8 weeks of aerobic exercise,compared with IR-Sed group,the weight,FINS,FPG,HOMA-IR and AUC_(BG) in IR-Ex group were decreased(P<0.01),and the ISI,glucose and insulin tolerance were increased(P<0.01).At the same time,compared with Con-Sed group,IR-Sed group had steatosis in hepatocyte,increased liver TG and serum ALT,AST contents(P<0.01),PAS staining was thin and uneven,liver glycogen content decreased(P<0.01);PEPCK,G6 Pase and FoxO1 protein contents increased(P<0.05);FNDC5,Irisin,p-Akt and p-FoxO1 protein levels decreased(P<0.05).After 8 weeks of aerobic exercise,compared with IR-Sed group,the steatosis in hepatocyte of IR-Ex group was improved,the contents of liver TG,serum ALT and AST were decreased(P<0.01),PAS staining was relatively full and uniform,the content of liver glycogen was increased(P<0.05),PEPCK and G6 Pase protein contents decreased(P <0.01);FNDC5,Irisin,p-Akt and p-FoxO1 protein levels increased(P<0.01).Conclusion Long-term aerobic exercise can effectively inhibit hepatic gluconeogenesis and improve IR,which may be related to the activation of Akt protein in liver tissue by FNDC5/Irisin,then promote the phosphorylation of FoxO1,further inhibiting the expression of PEPCK and G6 Pase to improve liver function.
作者 牟川 陈庆果 MOU Chuan;CHEN Qingguo(College of Physical Education,Sichuan Normal University,Chengdu 610101,China)
出处 《西安体育学院学报》 CSSCI 北大核心 2022年第3期345-354,共10页 Journal of Xi'an Physical Education University
基金 国家体育总局重点科研项目(2014B039)。
关键词 有氧运动 胰岛素抵抗 糖异生 FNDC5/Irisin 肝脏 aerobic exercise insulin resistance gluconeogenesis FNDC5/Irisin liver
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