G蛋白偶联胆汁酸受体
内科学
内分泌学
胰岛素抵抗
脂肪组织
兴奋剂
化学
受体
肥胖
药理学
医学
作者
Lili Ding,Qiaoling Yang,Eryun Zhang,Yangmeng Wang,Siming Sun,Yingbo Yang,Ting Tian,Zhengcai Ju,Lixian Jiang,Xunjiang Wang,Wendong Huang,Li Yang
标识
DOI:10.1016/j.apsb.2021.03.038
摘要
Obesity and its associated complications are highly related to a current public health crisis around the world. A growing body of evidence has indicated that G-protein coupled bile acid (BA) receptor TGR5 (also known as Gpbar-1) is a potential drug target to treat obesity and associated metabolic disorders. We have identified notoginsenoside Ft1 (Ft1) from Panax notoginseng as an agonist of TGR5 in vitro. However, the pharmacological effects of Ft1 on diet-induced obese (DIO) mice and the underlying mechanisms are still elusive. Here we show that Ft1 (100 mg/100 diet) increased adipose lipolysis, promoted fat browning in inguinal adipose tissue and induced glucagon-like peptide-1 (GLP-1) secretion in the ileum of wild type but not Tgr5-/- obese mice. In addition, Ft1 elevated serum free and taurine-conjugated bile acids (BAs) by antagonizing Fxr transcriptional activities in the ileum to activate Tgr5 in the adipose tissues. The metabolic benefits of Ft1 were abolished in Cyp27a1-/- mice which have much lower BA levels. These results identify Ft1 as a single compound with opposite activities on two key BA receptors to alleviate high fat diet-induced obesity and insulin resistance in mice.
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