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

作　　者：Yan-yan Yu Shi-chao Cui Tian-nan Zheng Hai-jian Ma Zhi-fu Xie Hao-wen Jiang Yu-feng Li Ke-xin Zhu Cheng-gang Huang Jia Li Jing-ya Li 

机构地区：[1]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [2]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Acta Pharmacologica Sinica》2021年第2期272-281,共10页中国药理学报（英文版）

基　　金：supported by grants from the Ministry of Science and Technology(2018ZX09711002-018 and 2016YFC1305505)and the National Natural Science Foundation of China(81673493).

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-κB 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.

关 键 词：insulin resistance SARSASAPOGENIN adipose tissue inflammation macrophage-adipocyte crosstalk IKK/NF-κB JNK 

分 类 号：R96[医药卫生—药理学]