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Selective PPAR gamma modulator diosmin improves insulin sensitivity and promotes browning of white fat

文献类型：期刊论文

作者Yu, Jian4,5,6,7; Hu, Yepeng4; Sheng, Maozheng5,6; Gao, Mingyuan5,6; Guo, Wenxiu5,6; Zhang, Zhe5,6; Wang, Dongmei5,6; Wu, Xia5,6; Li, Jin2; Chen, Yantao3
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
出版日期2023-04-01
卷号299期号:4页码:14
DOI10.1016/j.jbc.2023.103059
通讯作者Xu, Lingyan(lyxu@bio.ecnu.edu.cn) ; Gu, Xuejiang(guxuejiang@wmu.edu.cn) ; Ma, Xinran(xrma@bio.ecnu.edu.cn)
英文摘要Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipocyte differentiation, glucolipid metabolism, and inflammation. Thiazolidinediones are PPAR gamma full agonists with potent insulin-sensitizing effects, whereas their oral usage is restricted because of unwanted side effects, including obesity and cardiovascular risks. Here, via virtual screening, microscale thermophoresis analysis, and molecular confirmation, we demonstrate that diosmin, a natural com-pound of wide and long-term clinical use, is a selective PPAR gamma modulator that binds to PPAR gamma and blocks PPAR gamma phos-phorylation with weak transcriptional activity. Local diosmin administration in subcutaneous fat (inguinal white adipose tissue [iWAT]) improved insulin sensitivity and attenuated obesity via enhancing browning of white fat and energy expenditure. Besides, diosmin ameliorated inflammation in WAT and liver and reduced hepatic steatosis. Of note, we determined that iWAT local administration of diosmin did not exhibit obvious side effects. Taken together, the present study demonstrated that iWAT local delivery of diosmin protected mice from diet-induced insulin resistance, obesity, and fatty liver by blocking PPAR gamma phosphorylation, without apparent side effects, making it a potential therapeutic agent for the treatment of metabolic diseases.
WOS关键词ADIPOSE-TISSUE ; BEIGE FAT ; ACTIVATION ; MICE ; THIAZOLIDINEDIONES ; PHOSPHORYLATION ; ADIPOCYTES ; JUICES ; PRDM16 ; CELL
资助项目National Key Research and Development Program China[2019YFA09004500] ; National Natural Science Foundation of China[32022034] ; National Natural Science Foundation of China[32222024] ; National Natural Science Foundation of China[32271224] ; National Natural Science Foundation of China[32071148] ; Science and Technology Commission of Shanghai Municipality[22ZR1421200] ; Science and Technology Commission of Shanghai Municipality[21140904300] ; Natural Science Foundation of Chongqing, China[CSTB2022NSCQ-JQX0033] ; Key Research and Development Project of Zhejiang Province[2021C03069] ; Natural Science Foundation of Zhejiang Province[LY20H070003] ; ECNU public platform for Innovation[011]
WOS研究方向Biochemistry & Molecular Biology
语种英语
出版者ELSEVIER
WOS记录号WOS:001011180400001
源URL[http://119.78.100.183/handle/2S10ELR8/306319]  
专题新药研究国家重点实验室
通讯作者Xu, Lingyan; Gu, Xuejiang; Ma, Xinran
作者单位1.East China Normal Univ, Chongqing Key Lab Precis Opt, Chongqing Inst, Chongqing, Peoples R China
2.Shanghai Univ, Inst Cardiovasc Sci, Cardiac Regenerat & Ageing Lab, Sch Life Sci, Shanghai, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Ctr Chem Biol,State Key Lab Drug Res, Shanghai, Peoples R China
4.Wenzhou Med Univ, Affiliated Hosp 1, Dept Endocrine & Metab Dis, Wenzhou, Zhejiang, Peoples R China
5.East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai, Peoples R China
6.East China Normal Univ, Sch Life Sci, Shanghai, Peoples R China
7.Fengxian Dist Cent Hosp, Joint Ctr Translat Med, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Yu, Jian,Hu, Yepeng,Sheng, Maozheng,et al. Selective PPAR gamma modulator diosmin improves insulin sensitivity and promotes browning of white fat[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2023,299(4):14.
APA Yu, Jian.,Hu, Yepeng.,Sheng, Maozheng.,Gao, Mingyuan.,Guo, Wenxiu.,...&Ma, Xinran.(2023).Selective PPAR gamma modulator diosmin improves insulin sensitivity and promotes browning of white fat.JOURNAL OF BIOLOGICAL CHEMISTRY,299(4),14.
MLA Yu, Jian,et al."Selective PPAR gamma modulator diosmin improves insulin sensitivity and promotes browning of white fat".JOURNAL OF BIOLOGICAL CHEMISTRY 299.4(2023):14.

入库方式： OAI收割

来源：上海药物研究所

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