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

Zoological Research

Xin-Xin Zhan¹  Huai-Bin Zhou¹  Jian-Xin Lyu¹  Hai-Feng Chen¹  Yi Zheng¹  Qing-Lin Dang¹  Kun Zhang¹  He-Zhi Fang¹  Yue Yang¹  Qiong-Ya Zhao²  Ling-Hong Ge³ 

[1] Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China;School of Laboratory Medicine, Hangzhou Medical College, Hangzhou, Zhejiang 310053, China;Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, China;

关键词: obesity;    mitochondria;    metabolic dysfunction-associated fatty liver disease;    hepatic steatosis;    steatohepatitis;   

DOI  :  10.24272/j.issn.2095-8137.2020.051

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown