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Pyrazolone derivative C29 protects against HFD-induced obesity in mice via activation of AMPK in adipose tissue

文献类型：期刊论文

作者Li, Bo-han1,2; Zhang, Mei1; Duan, Ya-nan1; Shuai, Lin1; Jiang, Hao-wen1; Li, Jia1,2; Nan, Fa-jun1; Li, Jing-ya1
刊名ACTA PHARMACOLOGICA SINICA
出版日期2020-09-15
页码11
关键词AMP-activated protein kinase pyrazolone derivative C29 obesity energy expenditure thermogenesis inguinal white adipose tissue white adipose browning
ISSN号1671-4083
DOI10.1038/s41401-020-00524-0
通讯作者Nan, Fa-jun(fjnan@simm.ac.cn) ; Li, Jing-ya(jyli@simm.ac.cn)
英文摘要Beige adipocytes have been considered as a potential strategy in anti-obesity therapy because of its thermogenic capacity. AMP-activated protein kinase (AMPK) plays important roles in regulating adipose tissue function. C29 is a novel pyrazolone derivative with AMPK activity. In the current study, we investigated the role of C29 in the regulation of thermogenesis using differentiated adipocytes and diet-induced obese mice, and explored the mechanisms that might be involved in energy expenditure via adipocyte AMPK activation. We showed that treatment with C29 (2.5-10 mu M) concentration-dependently increased thermogenesis in differentiated preadipocytes separated from inguinal white adipose tissue (iWAT), evidenced by increased expression levels of thermogenesis markers such asUcp1,Pgc-1 alpha,Dio2,Prdm16,Cox7a1,Cox8b,Elovl3,andCidea, fatty acid oxidation (FAO) genes includingCpt1a,LcadandPpar alpha, as well as beige-selective genes such asCd137,Tmem26,Slc27a1,andTbx1. In high-fat diet (HFD)-fed mice, oral administration of C29 (30 mg center dot kg(-1)center dot day(-1)) for 9 weeks alleviated HFD-induced obesity, promoted energy expenditure and modulated iWAT browning. However, these effects were not observed in adipose-specific AMPK alpha 1/alpha 2 knockout (AKO) mice following C29 administration. Together, this study demonstrates that C29 regulates energy balance via adipocyte AMPK. Our findings show that the discovery of AMPK activators that specifically target adipose tissue may have therapeutic potential for treating obesity-related metabolic diseases.
WOS关键词BROWN-FAT ; GLUCOSE-HOMEOSTASIS ; INSULIN SENSITIVITY ; SKELETAL-MUSCLE ; ENERGY-BALANCE ; BEIGE ; THERMOGENESIS ; ADIPOCYTES ; PHOSPHORYLATION ; METABOLISM
资助项目National Natural Science Foundation of China[81470166] ; National Natural Science Foundation of China[81273566] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program of China[2018ZX09711002]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000569557900001
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/291189]  
专题新药研究国家重点实验室
通讯作者Nan, Fa-jun; Li, Jing-ya
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Drug Screening Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Li, Bo-han,Zhang, Mei,Duan, Ya-nan,et al. Pyrazolone derivative C29 protects against HFD-induced obesity in mice via activation of AMPK in adipose tissue[J]. ACTA PHARMACOLOGICA SINICA,2020:11.
APA Li, Bo-han.,Zhang, Mei.,Duan, Ya-nan.,Shuai, Lin.,Jiang, Hao-wen.,...&Li, Jing-ya.(2020).Pyrazolone derivative C29 protects against HFD-induced obesity in mice via activation of AMPK in adipose tissue.ACTA PHARMACOLOGICA SINICA,11.
MLA Li, Bo-han,et al."Pyrazolone derivative C29 protects against HFD-induced obesity in mice via activation of AMPK in adipose tissue".ACTA PHARMACOLOGICA SINICA (2020):11.

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来源：上海药物研究所

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