Hepatic Suppression of Mitochondrial Complex II Assembly Drives Systemic Metabolic Benefits
Abstract: Alternate day fasting (ADF), the most popular form of caloric restriction, has shown to improve metabolic health in preclinical subjects, while intrinsic network underpinning the process remains unclear. Here, it is found that liver undergoes dramatic metabolic reprogramming during ADF, accompanied surprisingly with unique complex II dysfunction attributing to suspended complex II assembly via suppressing SDHAF4, a recently identified assembly factor. Despite moderate mitochondrial complex II dysfunction, hepatic Sdhaf4 knockout mice present intriguingly improved glucose tolerance and systemic insulin sensitivity, consistent with mice after ADF intervention. Mechanistically, it is found that hepatocytes activate arginine‐nitric oxide (NO) biosynthesis axle in response to complex II and citric acid cycle dysfunction, the release of NO from liver can target muscle and adipocytes in addition to its autocrine action for enhanced insulin sensitivity. These results highlight the pivotal role of liver in ADF‐associated systemic benefits, and suggest that targeting hepatic complex II assembly can be an intriguing strategy against metabolic disorders.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Hepatic Suppression of Mitochondrial Complex II Assembly Drives Systemic Metabolic Benefits ; day:17 ; month:01 ; year:2022 ; extent:16
Advanced science ; (17.01.2022) (gesamt 16)
- Creator
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Wang, Xueqiang
Lv, Weiqiang
Xu, Jie
Zheng, Adi
Zeng, Mengqi
Cao, Ke
Wang, Xun
Cui, Yuting
Li, Hao
Yang, Meng
Shao, Yongping
Zhang, Fang
Zou, Xuan
Long, Jiangang
Feng, Zhihui
Liu, Jiankang
- DOI
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10.1002/advs.202105587
- URN
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urn:nbn:de:101:1-2022011714160026533130
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:24 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Wang, Xueqiang
- Lv, Weiqiang
- Xu, Jie
- Zheng, Adi
- Zeng, Mengqi
- Cao, Ke
- Wang, Xun
- Cui, Yuting
- Li, Hao
- Yang, Meng
- Shao, Yongping
- Zhang, Fang
- Zou, Xuan
- Long, Jiangang
- Feng, Zhihui
- Liu, Jiankang
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