Elaiophylin reduces body weight and lowers glucose levels in obese mice by activating AMPK

作者全名："Bao, Ruoxuan; Meng, Yongmei; Zhang, Haibo; Yang, Chen; Li, Wei; Zhang, Cheng; Zhang, Jinye; Sun, Renqiang; Li, Zengxia; Jiang, Wei; Zhang, Chensong; Zhang, Changsheng; Yuan, Hai-Xin; Dang, Yongjun"

作者地址："[Bao, Ruoxuan; Zhang, Cheng; Zhang, Jinye; Sun, Renqiang; Yuan, Hai-Xin] Fudan Univ, Mol & Cell Biol Res Lab, Inst Biomed Sci, Shanghai 200032, Peoples R China; [Bao, Ruoxuan; Zhang, Cheng; Zhang, Jinye; Sun, Renqiang; Yuan, Hai-Xin] Fudan Univ, Sch Basic Med Sci, Shanghai 200032, Peoples R China; [Meng, Yongmei] Inner Mongolia Med Univ, Coll Tradit Mongolian Med, Mongolia 010110, Peoples R China; [Zhang, Haibo; Zhang, Changsheng] South China Sea Inst Oceanol, Inst South China Sea Ecol & Environm Engn, Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med,Chinese Acad Sci, Guangzhou 510301, Guangdong, Peoples R China; [Yang, Chen; Li, Zengxia; Jiang, Wei; Dang, Yongjun] Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Key Lab Metab & Mol Med,Minist Educ, Shanghai 200031, Peoples R China; [Li, Wei] China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China; [Zhang, Chensong] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China; [Dang, Yongjun] Chongqing Med Univ, Inst Life Sci, Ctr Novel Target & Therapeut Intervent, Chongqing 400016, Peoples R China"

通信作者："Yuan, HX (corresponding author), Fudan Univ, Mol & Cell Biol Res Lab, Inst Biomed Sci, Shanghai 200032, Peoples R China.; Yuan, HX (corresponding author), Fudan Univ, Sch Basic Med Sci, Shanghai 200032, Peoples R China.; Zhang, CS (corresponding author), South China Sea Inst Oceanol, Inst South China Sea Ecol & Environm Engn, Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med,Chinese Acad Sci, Guangzhou 510301, Guangdong, Peoples R China.; Dang, YJ (corresponding author), Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Key Lab Metab & Mol Med,Minist Educ, Shanghai 200031, Peoples R China.; Dang, YJ (corresponding author), Chongqing Med Univ, Inst Life Sci, Ctr Novel Target & Therapeut Intervent, Chongqing 400016, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000709405900002

JCR分区：Q1

影响因子：9

年份：2021

卷号：12

期号：11

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Obesity is an epidemic affecting 13% of the global population and increasing the risk of many chronic diseases. However, only several drugs are licensed for pharmacological intervention for the treatment of obesity. As a master regulator of metabolism, the therapeutic potential of AMPK is widely recognized and aggressively pursued for the treatment of metabolic diseases. We found that elaiophylin (Ela) rapidly activates AMPK in a panel of cancer-cell lines, as well as primary hepatocytes and adipocytes. Meanwhile, Ela inhibits the mTORC1 complex, turning on catabolism and turning off anabolism together with AMPK. In vitro and in vivo studies showed that Ela does not activate AMPK directly, instead, it increases cellular AMP/ATP and ADP/ATP ratios, leading to AMPK phosphorylation in a LKB1-dependent manner. AMPK activation induced by Ela caused changes in diverse metabolic genes, thereby promoting glucose consumption and fatty acid oxidation. Importantly, Ela activates AMPK in mouse liver and adipose tissue. As a consequence, it reduces body weight and blood glucose levels and improves glucose and insulin tolerance in both ob/ob and high-fat diet-induced obese mouse models. Our study has identified a novel AMPK activator as a candidate drug for the treatment of obesity and its associated chronic diseases."

基金机构："National Key Research and Development Program of China [2018YFA0800304, 2018YFC0310900]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21877016, 81820108030, 31970684, 81773190, 21977115]; Development Fund for Shanghai Talents [2019109]"

基金资助正文："This work was supported by the National Key Research and Development Program of China (no. 2018YFA0800304 to H.-X. Y., 2018YFC0310900 to Y.D.), the National Natural Science Foundation of China (no. 21877016, 81820108030 to Y.D., 31970684, 81773190 to H.-X. Y., and 21977115 to W.L.), and the Development Fund for Shanghai Talents (no. 2019109 to H.-X. Y.)."