Role of aerobic exercise in ameliorating NASH: Insights into the hepatic thyroid hormone signaling and circulating thyroid hormones.

Role of aerobic exercise in ameliorating NASH: Insights into the hepatic thyroid hormone signaling and circulating thyroid hormones.
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有氧运动在改善 NASH 中的作用:深入了解肝甲状腺激素信号传导和循环甲状腺激素

DOI:
10.3389/fendo.2022.1075986
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发表时间:
2022
影响因子:
5.2
通讯作者:
Li, Xuejun
Li, Xuejun
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Qiuhong;Li, Han;He, Weiwei;Zhao, Qing;Huang, Caoxin;Wang, Qingxuan;Zheng, Zeyu;Zhang, Xiaofang;Shi, Xiulin;Li, Xuejun

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目的三碘甲腺原氨酸(T3)可显著消除肝脏脂肪变性,对非酒精性脂肪性肝炎(NASH)有一定的治疗作用。然而,T3介导的运动改善NASH的潜在机制尚不清楚。本研究旨在探讨有氧运动对非酒精性脂肪肝患者肝损伤的影响。方法采用有氧运动的方法,观察有氧运动对动脉粥样硬化(Ath)饮食诱导的NASH肝损伤的影响。采用生化评价、组织学染色和实时定量聚合酶链式反应(Real-Time-PCR)等方法证实运动对NASH的改善作用。对各组肝脏进行RNA测序(RNA-seq)分析,进一步确定有氧运动的潜在机制。应用生物信息学方法探讨有氧运动改善NASH小鼠肝组织功能的关键途径。结果有氧运动可改善NASH小鼠肝脏脂肪变性、小叶炎症和纤维化。NASH组大鼠肝脏内多种炎症相关途径明显丰富,有氧运动可改善肝脏炎症反应。基因集变异分析(GSVA)结果显示,运动后NASH小鼠的T3反应信号具有较高的富集度。运动后NASH小鼠肝脏Dio1表达增加,有氧运动后循环FT3、FT4水平升高。结论有氧运动可显著减轻NASH小鼠肝脏脂质堆积、炎性细胞浸润和肝纤维化进展。肝脏甲状腺激素信号的激活和循环中的甲状腺激素可能参与了特技运动对NASH进展的改善作用。
Aim Triiodothyronine (T3) administration significantly eliminates hepatic steatosis and also has a therapeutic effect on non-alcoholic steatohepatitis (NASH). However, the potential mechanism by which T3-mediated exercise improves NASH is unknow. This study aimed to explore the effect of aerobic exercise on liver injury in NASH. Methods Aerobic exercise was conducted to explore the effects of exercise on liver injury in NASH model induced by Atherosclerotic (Ath) diet. Biochemical evaluations, histological staining and real-time PCR were first applied to confirm the amelioration effects of exercise on NASH. RNA-sequencing (RNA-seq) analysis for livers of each group were further used to identify the underlying mechanisms of aerobic exercise. Bioinformatics methods were used to explore the key functional pathways involved in the improvement of liver tissue in NASH mice by aerobic exercise. Results Aerobic exercise improved hepatic steatosis, lobular inflammation and fibrosis in NASH mice. multiple inflammation-related pathways were significantly enriched in the liver of NASH group and improved by aerobic exercise. The results of gene set variation analysis (GSVA) showed a higher enrichment score of T3 response signature in NASH mice with exercise. Increased Dio1 expression in the liver of NASH with exercise mice and increased circulating FT3 and FT4 levels upon aerobic exercise were confirmed. Conclusions We found that aerobic exercise could significantly reduce hepatic lipid accumulation, inflammatory infiltration and fibrosis progression in the liver of NASH mice. Hepatic thyroid hormone signaling activation and circulating thyroid hormones is potentially involved in the amelioration effect of aerobatic exercise on NASH progression.
DOI: 10.1038/s41591-018-0104-9
发表时间: 2018-07
期刊: Nature medicine
影响因子: 82.9
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