Gadd45b is required in part for the anti-obesity effect of constitutive androstane receptor(CAR)

作     者：Xinran Cai Ye Feng Meishu Xu Chaohui Yu Wen Xie Xinran Cai;Ye Feng;Meishu Xu;Chaohui Yu;Wen Xie

作者机构：Center for Pharmacogenetics and Department of Pharmaceutical SciencesUniversity of PittsburghPittsburghPA 15261USA Department of Endocrinology and Metabolic Diseasethe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Gastroenterologythe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Pharmacology and Chemical BiologyUniversity of PittsburghPittsburghPA 15261USA 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第2期

页      面：434-441页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported in part by the Joseph Koslow Endowed Professorship from the University of Pittsburgh School of Pharmacy(Pittsburgh PA USA) 

主　　题：Obesity Diabetes CAR Gadd45b Glucogenogenesis Lipogenesis Xenobiotics Nuclear receptor 

摘      要：Crosstalk between xenobiotic metabolism and energy metabolism in the liver has provided a potential opportunity to target xenobiotic receptors to treat metabolic *** of constitutive andro stane receptor(CAR),a xenobiotic-sensing nuclear receptor,has been shown to inhibit obesity,suppress hepatic gluconeogenesis,and ameliorate hyperglycemia in rodent models of obesity and type 2 ***,the underlying molecular mechanism remains to be *** growth arrest and DNA damage-inducible gene 45 b(Gadd45 b),a well-known anti-apoptotic factor,has been shown to be an inducible coactivator of CAR in promoting rapid liver *** is unknown whether the effect of CAR on energy metabolism depends on GADD45 *** the present study and by using a high fat diet(HFD)-induced obesity model,we show that reduced body weight gain and improved insulin sensitivity by the CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene(TCPOBOP)were markedly blunted in Gadd45 b knockout ***,the TCPOBOP-responsive inhibition of hepatic lipogenesis,gluconeogenesis,and adipose inflammation observed in wild type mice were largely abolished in Gadd45 b knockout *** conclude that Gadd45 b is required in part for the metabolic benefits of CAR activation.