PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling

doi:10.1038/s41467-021-23285-8

	PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling
	Ma, Ning 1; Wang, Yi-Kang 1; Xu, Sheng 1; Ni, Qian-Zhi 1; Zheng, Qian-Wen1,2 ; Zhu, Bing 1; Cao, Hui-Jun 1; Jiang, Hao 1; Zhang, Feng-Kun 1; Yuan, Yan-Mei 1; Zhang, Er-Bin 1; Chen, Tian-Wei 1; Xia, Ji 1; Ding, Xu-Fen 1; Chen, Zhen-Hua 3; Zhang, Xiu-Ping 4; Wang, Kang 3; Cheng, Shu-Qun 3; Qiu, Lin 1; Li, Zhi-Gang 5; Yu, Yong-Chun 6; Wang, Xiao-Fan 7; Zhou, Bin 8; Li, Jing-Jing 1; Xie, Dong1,2,9
	2021
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
ISSN	2041-1723
卷号	12 期号:1
DOI	10.1038/s41467-021-23285-8
摘要	Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in the world, however, no drug treatment has been approved for this disease. Thus, it is urgent to find effective therapeutic targets for clinical intervention. In this study, we find that liver-specific knockout of PPDPF (PPDPF-LKO) leads to spontaneous fatty liver formation in a mouse model at 32 weeks of age on chow diets, which is enhanced by HFD. Mechanistic study reveals that PPDPF negatively regulates mTORC1-S6K-SREBP1 signaling. PPDPF interferes with the interaction between Raptor and CUL4B-DDB1, an E3 ligase complex, which prevents ubiquitination and activation of Raptor. Accordingly, liver-specific PPDPF overexpression effectively inhibits HFD-induced mTOR signaling activation and hepatic steatosis in mice. These results suggest that PPDPF is a regulator of mTORC1 signaling in lipid metabolism, and may be a potential therapeutic candidate for NAFLD. Non-alcoholic fatty liver disease (NAFLD) has become a prevalent chronic liver disease, however, drugs to treat this disease are still lacking. Here, the authors show that PPDPF inhibits the development of hepatic steatosis by negatively regulating mTORC1-S6K-SREBP1 signaling, which provides a potential therapeutic candidate for NAFLD treatment.
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收录类别	SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000658769900011
出版者	NATURE RESEARCH
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/127618
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_谢东组
通讯作者	Li, Jing-Jing; Xie, Dong
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, 393 Middle Huaxia Rd, Shanghai, Peoples R China; 3.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 6, Shanghai, Peoples R China; 4.Chinese Peoples Liberat Army PLA Gen Hosp, Dept Hepatobiliary & Pancreat Surg Oncol, Med Ctr 1, Beijing, Peoples R China; 5.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Thorac Surg, Sect Esophageal Surg, Shanghai, Peoples R China; 6.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai Inst Thorac Oncol, Shanghai, Peoples R China; 7.Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA; 8.Chinese Acad Sci, Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,State Key Lab C, Shanghai, Peoples R China; 9.China Natl Ctr Food Safety Risk Assessment, NHC Key Lab Food Safety Risk Assessment, Beijing, 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	Ma, Ning,Wang, Yi-Kang,Xu, Sheng,et al. PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling[J]. NATURE COMMUNICATIONS,2021,12(1).
APA	Ma, Ning.,Wang, Yi-Kang.,Xu, Sheng.,Ni, Qian-Zhi.,Zheng, Qian-Wen.,...&Xie, Dong.(2021).PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling.NATURE COMMUNICATIONS,12(1).
MLA	Ma, Ning,et al."PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling".NATURE COMMUNICATIONS 12.1(2021).