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Intermittent fasting promotes adipocyte mitochondrial fusion through Sirt3-mediated deacetylation of Mdh2

Published online by Cambridge University Press:  23 February 2023

Yizhou Li
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
Juntong Liang
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
Xin Tian
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
Qi Chen
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
Longbo Zhu
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
Han Wang
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
Zunhai Liu
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
Xulei Dai
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
Chenqi Bian
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
Chao Sun*
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
*Corresponding author: Dr C. Sun, fax +86 29 87092164, email


Fat deposition and lipid metabolism are closely related to the morphology, structure and function of mitochondria. The morphology of mitochondria between fusion and fission processes is mainly regulated by protein posttranslational modification. Intermittent fasting (IF) promotes high expression of Sirtuin 3 (Sirt3) and induces mitochondrial fusion in high-fat diet (HFD)-fed mice. However, the mechanism by which Sirt3 participates in mitochondrial protein acetylation during IF to regulate mitochondrial fusion and fission dynamics remains unclear. This article demonstrates that IF promotes mitochondrial fusion and improves mitochondrial function in HFD mouse inguinal white adipose tissue. Proteomic sequencing revealed that IF increased protein deacetylation levels in HFD mice and significantly increased Sirt3 mRNA and protein expression. After transfecting with Sirt3 overexpression or interference vectors into adipocytes, we found that Sirt3 promoted adipocyte mitochondrial fusion and improved mitochondrial function. Furthermore, Sirt3 regulates the JNK-FIS1 pathway by deacetylating malate dehydrogenase 2 (MDH2) to promote mitochondrial fusion. In summary, our study indicates that IF promotes mitochondrial fusion and improves mitochondrial function by upregulating the high expression of Sirt3 in HFD mice, promoting deacetylation of MDH2 and inhibiting the JNK-FIS1 pathway. This research provides theoretical support for studies related to energy limitation and animal lipid metabolism.

Research Article
© The Author(s), 2023. Published by Cambridge University Press on behalf of The Nutrition Society

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