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Intestinal MYC modulates obesity-related metabolic dysfunction

文献类型：期刊论文

作者Luo, Yuhong1; Yang, Shoumei1; Wu, Xuan2,3; Takahashi, Shogo1,4; Sun, Lulu1; Cai, Jie1; Krausz, Kristopher W.1; Guo, Xiaozhen5; Dias, Henrique B.1; Gavrilova, Oksana6
刊名NATURE METABOLISM
出版日期2021-07-01
页码37
DOI10.1038/s42255-021-00421-8
通讯作者Liu, Weiwei(hsvivian@tongji.edu.cn) ; Gonzalez, Frank J.(gonzalef@mail.nih.gov)
英文摘要MYC is a transcription factor with broad biological functions, notably in the control of cell proliferation. Here, we show that intestinal MYC regulates systemic metabolism. We find that MYC expression is increased in ileum biopsies from individuals with obesity and positively correlates with body mass index. Intestine-specific reduction of MYC in mice improves high-fat-diet-induced obesity, insulin resistance, hepatic steatosis and steatohepatitis. Mechanistically, reduced expression of MYC in the intestine promotes glucagon-like peptide-1 (GLP-1) production and secretion. Moreover, we identify Cers4, encoding ceramide synthase 4, catalysing de novo ceramide synthesis, as a MYC target gene. Finally, we show that administration of the MYC inhibitor 10058-F4 has beneficial effects on high-fat-diet-induced metabolic disorders, and is accompanied by increased GLP-1 and reduced ceramide levels in serum. This study positions intestinal MYC as a putative drug target against metabolic diseases, including non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Inhibition of intestinal MYC is shown to have beneficial metabolic effects by promoting GLP-1 secretion and reducing ceramide production.
WOS关键词GLUCAGON-LIKE PEPTIDE-1 ; C-MYC ; CERAMIDE METABOLISM ; PLASMA CERAMIDES ; 7-36 AMIDE ; EXPRESSION ; PROGRESSION ; HOMEOSTASIS ; CELLS ; NAFLD
资助项目National Cancer Institute Intramural Research Program[ZIA BC005562] ; Outstanding academic leaders plan of Shanghai[2018BR07] ; First Affiliated Hospital, University of Science and Technology of China
WOS研究方向Endocrinology & Metabolism
语种英语
出版者NATURE RESEARCH
WOS记录号WOS:000669993500003
源URL[http://119.78.100.183/handle/2S10ELR8/296805]  
专题新药研究国家重点实验室
通讯作者Liu, Weiwei; Gonzalez, Frank J.
作者单位1.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
2.Tongji Univ, Shanghai Peoples Hosp 10, Dept Lab Med & Cent Lab, Shanghai, Peoples R China
3.Tongji Univ, Shanghai Skin Dis Hosp, Dept Lab Med, Shanghai, Peoples R China
4.Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC USA
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
6.NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA
7.Peking Univ, Key Lab Mol Cardiovasc Sci, Minist Educ, Dept Physiol & Pathophysiol,Sch Basic Med Sci, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Luo, Yuhong,Yang, Shoumei,Wu, Xuan,et al. Intestinal MYC modulates obesity-related metabolic dysfunction[J]. NATURE METABOLISM,2021:37.
APA Luo, Yuhong.,Yang, Shoumei.,Wu, Xuan.,Takahashi, Shogo.,Sun, Lulu.,...&Gonzalez, Frank J..(2021).Intestinal MYC modulates obesity-related metabolic dysfunction.NATURE METABOLISM,37.
MLA Luo, Yuhong,et al."Intestinal MYC modulates obesity-related metabolic dysfunction".NATURE METABOLISM (2021):37.

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来源：上海药物研究所

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