PAQR9 regulates hepatic ketogenesis and fatty acid oxidation during fasting by modulating protein stability of PPAR alpha

doi:10.1016/j.molmet.2021.101331

	PAQR9 regulates hepatic ketogenesis and fatty acid oxidation during fasting by modulating protein stability of PPAR alpha
	Lin, Yijun 1; Chen, Lingling 1; You, Xue 1; Li, Zixuan 1; Li, Chenchen 1; Chen, Yan1,2
	2021-11
发表期刊	MOLECULAR METABOLISM (IF:7.0[JCR-2023],7.9[5-Year])
ISSN	2212-8778
卷号	53
DOI	10.1016/j.molmet.2021.101331
摘要	Background: The cycle of feeding and fasting is fundamental to life and closely coordinated with changes of metabolic programs. During extended starvation, ketogenesis coupled with fatty acid oxidation in the liver supplies ketone bodies to extrahepatic tissues as the major form of fuel. In this study, we demonstrated that PAQR9, a member of the progesterone and adipoQ receptor family, has a regulatory role on hepatic ketogenesis. Methods: We analyzed the phenotype of Paqr9-deleted mice. We also used biochemical methods to investigate the interaction of PAQR9 with PPARa and HUWE1, an E3 ubiquitin ligase. Results: The expression of Paqr9 was decreased during fasting partly depending on PPAR gamma. The overall phenotype of the mice was not altered by Paqr9 deletion under normal chow feeding. However, fasting-induced ketogenesis and fatty acid oxidation were attenuated by Paqr9 deletion. Mechanistically, Paqr9 deletion decreased protein stability of PPARa via enhancing its poly-ubiquitination. PAQR9 competed with HUWE1 for interaction with PPAR alpha, thus preventing ubiquitin-mediated degradation of PPAR alpha. Conclusion: Our study reveals that PAQR9 impacts starvation-mediated metabolic changes in the liver via post-translational regulation of PPAR alpha. (C) 2021 The Authors. Published by Elsevier GmbH.
关键词	PAQR9 PPAR alpha HUWE1 Starvation Ketogenesis Fatty acid oxidation
收录类别	SCIE
语种	英语
WOS研究方向	Endocrinology & Metabolism
WOS类目	Endocrinology & Metabolism
WOS记录号	WOS:000702820300007
出版者	ELSEVIER
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128291
专题	生命科学与技术学院_特聘教授组_陈雁组
通讯作者	Chen, Yan
作者单位	1.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Nutr Metab & Food Safety, Shanghai, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Lin, Yijun,Chen, Lingling,You, Xue,et al. PAQR9 regulates hepatic ketogenesis and fatty acid oxidation during fasting by modulating protein stability of PPAR alpha[J]. MOLECULAR METABOLISM,2021,53.
APA	Lin, Yijun,Chen, Lingling,You, Xue,Li, Zixuan,Li, Chenchen,&Chen, Yan.(2021).PAQR9 regulates hepatic ketogenesis and fatty acid oxidation during fasting by modulating protein stability of PPAR alpha.MOLECULAR METABOLISM,53.
MLA	Lin, Yijun,et al."PAQR9 regulates hepatic ketogenesis and fatty acid oxidation during fasting by modulating protein stability of PPAR alpha".MOLECULAR METABOLISM 53(2021).