Sarsasapogenin improves adipose tissue inflammation and ameliorates insulin resistance in high-fat diet-fed C57BL/6J mice

doi:10.1038/s41401-020-0427-1

	Sarsasapogenin improves adipose tissue inflammation and ameliorates insulin resistance in high-fat diet-fed C57BL/6J mice
	Yu, Yan-yan 1,2; Cui, Shi-chao 1; Zheng, Tian-nan 1,2; Ma, Hai-jian 1; Xie, Zhi-fu 1; Jiang, Hao-wen 1; Li, Yu-feng 1,2; Zhu, Ke-xin 1,2; Huang, Cheng-gang 1; Li, Jia 1
刊名	ACTA PHARMACOLOGICA SINICA
	2020-07-22
页码	10
关键词	insulin resistance sarsasapogenin adipose tissue inflammation macrophage-adipocyte crosstalk IKK/NF-kappa B JNK
ISSN号	1671-4083
DOI	10.1038/s41401-020-0427-1
通讯作者	Li, Jia(jli@simm.ac.cn) ; Li, Jing-ya(jyli@simm.ac.cn)
英文摘要	Insulin resistance is a major cause of type 2 diabetes and metabolic syndrome. Macrophage infiltration into obese adipose tissue promotes inflammatory responses that contribute to the pathogenesis of insulin resistance. Suppression of adipose tissue inflammatory responses is postulated to increase insulin sensitivity in obese patients and animals. Sarsasapogenin (ZGY) is one of the metabolites of timosaponin AIII in the gut, which has been shown to exert anti-inflammatory action. In this study, we investigated the effects of ZGY treatment on obesity-induced insulin resistance in mice. We showed that pretreatment with ZGY (80 mg.kg(-1).d(-1), ig, for 18 days) significantly inhibited acute adipose tissue inflammatory responses in LPS-treated mice. In high-fat diet (HFD)-fed obese mice, oral administration of ZGY (80 mg.kg(-1).d(-1), for 6 weeks) ameliorated insulin resistance and alleviated inflammation in adipose tissues by reducing the infiltration of macrophages. Furthermore, we demonstrated that ZGY not only directly inhibited inflammatory responses in macrophages and adipocytes, but also interrupts the crosstalk between macrophages and adipocytes in vitro, improving adipocyte insulin resistance. The insulin-sensitizing and anti-inflammatory effects of ZGY may result from inactivation of the IKK/NF-kappa B and JNK inflammatory signaling pathways in adipocytes. Collectively, our findings suggest that ZGY ameliorates insulin resistance and alleviates the adipose inflammatory state in HFD mice, suggesting that ZGY may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.
资助项目	Ministry of Science and Technology[2018ZX09711002-018] ; Ministry of Science and Technology[2016YFC1305505] ; National Natural Science Foundation of China[81673493]
WOS关键词	PARACRINE LOOP ; KAPPA-B ; OBESITY ; MACROPHAGES ; ADIPOCYTES ; ACTIVATION ; SENSITIVITY ; MECHANISMS ; RESPONSES ; KINASE
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000551409300002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292132]
专题	中国科学院上海药物研究所
通讯作者	Li, Jia; Li, Jing-ya
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Yu, Yan-yan,Cui, Shi-chao,Zheng, Tian-nan,et al. Sarsasapogenin improves adipose tissue inflammation and ameliorates insulin resistance in high-fat diet-fed C57BL/6J mice[J]. ACTA PHARMACOLOGICA SINICA,2020:10.
APA	Yu, Yan-yan.,Cui, Shi-chao.,Zheng, Tian-nan.,Ma, Hai-jian.,Xie, Zhi-fu.,...&Li, Jing-ya.(2020).Sarsasapogenin improves adipose tissue inflammation and ameliorates insulin resistance in high-fat diet-fed C57BL/6J mice.ACTA PHARMACOLOGICA SINICA,10.
MLA	Yu, Yan-yan,et al."Sarsasapogenin improves adipose tissue inflammation and ameliorates insulin resistance in high-fat diet-fed C57BL/6J mice".ACTA PHARMACOLOGICA SINICA (2020):10.