Effect of methionine/choline-deficient diet and high-fat diet-induced steatohepatitis on mitochondrial homeostasis in mice
Effect of methionine/choline-deficient diet and high-fat diet-induced steatohepatitis on mitochondrial homeostasis in mice
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DOI：
10.1016/j.bbrc.2020.03.180
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发表时间：
2020-06-25
影响因子：
3.1
通讯作者：
Terai, Shuji
中科院分区：
文献类型：
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作者：
Arao, Yoshihisa;Kawai, Hirokazu;Terai, Shuji
考虑到非酒精性脂肪性肝炎(NASH)病例的增加，使用合适的NASH动物模型对于了解其潜在的发病机制是至关重要的。到目前为止，已经使用了几种小鼠模型；然而，病因和所用食物的显著差异影响了结果，结论不一致。因此，有必要了解这些模型及其差异，以便能够选择合适的模型。受人类非酒精性脂肪性肝病线粒体DNA含量改变的启发，我们研究了高脂饮食(HFD)和蛋氨酸/胆碱缺乏饮食(MCD)诱导的NASH小鼠模型线粒体DNA拷贝数的变化，以了解这两种模型之间的差异。MCD组和HFD组均可见大线粒体。而MCD组大鼠肝脏mtDNA含量明显低于HFD组。这些变化与线粒体生物发生和降解相关基因在MCD模型中较HFD模型显著上调有关。因此，线粒体DNA的稳定性与研究中经常使用的MCD和HFD诱导的NASH模型之间的差异有关；这些发现有助于为NASH研究选择合适的模型。(C)2020 Elsevier Inc.保留所有权利。
Considering the increase in cases of non-alcoholic steatohepatitis (NASH), the use of appropriate animal model of NASH is essential to understand the underlying pathogenesis mechanism. To date, several mice models have been used; however, significant differences in the etiologies and food administered affected the results, with inconsistent conclusions. Therefore, it is necessary to understand these models and their differences to be able to choose appropriate models. Inspired by the fact that mitochondrial (mt)DNA content is changed in non-alcoholic fatty liver disease in humans, we investigated the mtDNA copy number in the NASH mice models induced by high-fat diet (HFD) and methionine/choline-deficient diet (MCD) to understand the differences between these models. Megamitochondria were observed in both MCD and HFD groups. However, the MCD group showed significant decrease in liver mtDNA content compared with that in the HFD group. These changes were associated with significant upregulation of mitochondrial biogenesis- and degradation-related genes in MCD model than in HFD model. Thus, stability of mtDNA is associated with the differences between MCD and HFD-induced NASH models often used in studies; these findings could help in choosing appropriate models for studies on NASH. (C) 2020 Elsevier Inc. All rights reserved.