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. 2020 Sep 18;41(5):539-551.
doi: 10.24272/j.issn.2095-8137.2020.051.

Assessment of mitochondrial function in metabolic dysfunction-associated fatty liver disease using obese mouse models

Qiong-Ya Zhao  1   2 , Ling-Hong Ge  3 , Kun Zhang  2 , Hai-Feng Chen  2 , Xin-Xin Zhan  2 , Yue Yang  2 , Qing-Lin Dang  2 , Yi Zheng  2 , Huai-Bin Zhou  2 , Jian-Xin Lyu  4 , He-Zhi Fang  5
Affiliations

Assessment of mitochondrial function in metabolic dysfunction-associated fatty liver disease using obese mouse models

Qiong-Ya Zhao et al. Zool Res. .

Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD) is characterized by deregulated hepatic lipid metabolism; however, the association between MAFLD development and mitochondrial dysfunction has yet to be confirmed. Herein, we employed high-resolution respirometry, blue native polyacrylamide gel electrophoresis-based in-gel activity measurement and immunoblot analysis to assess mitochondrial function in obesity-induced mouse models with varying degrees of MAFLD. Results showed a slight but significant decrease in hepatic mitochondrial respiration in some MAFLD mice compared to mice fed a standard diet. However, the activities and levels of mitochondrial oxidative phosphorylation complexes remained unchanged during obesity-induced MAFLD progression. These results suggest that mitochondrial function, particularly oxidative phosphorylation, was mildly affected during obesity-induced MAFLD development. Moreover, transcriptome profiling of mouse and human liver tissues with varying degrees of MAFLD revealed that the decreased activation of mitochondria-related pathways was only associated with MAFLD of a high histological grade, whereas the major regulators of mitochondrial biogenesis were not altered in mice or humans during MAFLD development. Collectively, our results suggest that impaired hepatic mitochondrial function is not closely associated with obesity-induced MAFLD. Therefore, therapeutic strategies targeting mitochondria for the treatment of MAFLD should be reconsidered.

Keywords: Hepatic steatosis; Metabolic dysfunction-associated fatty liver disease; Mitochondria; Obesity; Steatohepatitis.

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Figures

Figure 1
Figure 1. Establishment of diet-induced models of NASH
Figure 2
Figure 2. Oxidative stress and antioxidant markers during NASH progression
Figure 3
Figure 3. Hepatic mitochondrial function during NASH progression
Figure 4
Figure 4. Hepatic transcriptome profiling during NASH progression
Figure 5
Figure 5. Hepatic transcriptome analysis of public human NASH dataset
See this image and copyright information in PMC

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