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

Abstract

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.

Keywords: High-fat diet; Methionine/choline-deficient diet; Mitochondrial DNA copy Number; Mitochondrial biogenesis; Mitochondrial degradation; Oxidative stress.