Effect of methionine/choline-deficient diet and high-fat diet-induced steatohepatitis on mitochondrial homeostasis in mice.

Yoshihisa Arao, Hirokazu Kawai, Kenya Kamimura, Takamasa Kobayashi, Oki Nakano, Manabu Hayatsu, Tatsuo Ushiki, Shuji Terai

Biochemical and biophysical research communications 2020 Jun 25

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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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Yoshihisa Arao, Hirokazu Kawai, Kenya Kamimura, Takamasa Kobayashi, Oki Nakano, Manabu Hayatsu, Tatsuo Ushiki, Shuji Terai. Effect of methionine/choline-deficient diet and high-fat diet-induced steatohepatitis on mitochondrial homeostasis in mice. Biochemical and biophysical research communications. 2020 Jun 25;527(2):365-371