Resveratrol derivative BTM-0512 mitigates obesity by promoting beige remodeling of subcutaneous preadipocytes  

作　　者：Qingqing Li Kuansong Wang Yipeng Ma Chunxiang Qin Changsheng Dong Ping Jin Yan Wu Xiaoming Xiong Niansheng Li Changping Hu Jun Peng Zhichun Yang 

机构地区：[1]Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China [2]Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China [3]Department of Pathology, School of Basic Medicine, Central South University, Changsha 410008, China [4]Department of Obstetrics and Gynecology, the Third Xiangya Hospital, Central South University, Changsha 410013, China [5]Division of Anesthetic, the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, China [6]Department of Endocrinology, the Third Xiangya Hospital, Central South University, Changsha 410013, China [7]Hunan Provincial Key Laboratory of Cardiovascular Research, Changsha 410078. China

出　　处：《Acta Biochimica et Biophysica Sinica》2017年第4期318-327,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China （Nos. 81001464, 81373409, and 81673491）, the Natural Science Foundation of Hunan Province （Nos. 2015JJ3140, 2015JJ2150, and 13JJ2008）, and the Teacher＇s Funding of Central South University （No. 2014JSJJ029）.

摘　　要：Recent studies revealed that sirtuin 1 （SIRT1） is involved in the regulation of energy metabolism and its agonist resveratrol showed anti-obesity effect. This study aims to determine whether BTM- 0512, a novel derivative of resveratrol, acts as an antagonist of obesity and to explore its possible mechanisms. High-fat diet （HFD）-induced obese mice were intragastrically administered with BTM-0512 （5, 10, and 20 mg/kg/day） or resveratrol （10mg/kg/day）. It was found that the body weight, Lee＇s index, ratio of visceral adipose tissue （VAT） to body weight, and blood glucose were significantly reduced in BTM-0512-treated mice when compared with those in mice treated with resveratrol. BTM-0512 up-regulated the expressions of SIRT1, full length PRDM16 （fPRDM16）, total PRDM16 （tPRDM16, including fPPRDM16 and other PRDM16 isoforms）, and uncoupling protein 1 （UCP1） in both brown and subcutaneous adipose tissues. Although BTM-0512 and resveratrol also up-regulated SIRT1 and tPRDM16 levels in VAT of HFD-induced obese mice, the expressions of fPRDM16, UCP1, and TMEM26 were down-regulated. In mouse primary subcutaneous preadipo- cytes cultured with or without adipogenic medium, BTM-0512 up-regulated fPRDM16, tPRDM16, and UCP1 expressions, which was reversed by SIRT1 antagonists. But in cultured brown and visceral adipocytes, the UCP1 protein level showed no significant change after treatment with 1 μM of BTM-0512. Moreover, transfection with human SIRT1 plasmid reduced lipid deposit, as well as the mRNA levels of fPRDM16, UCP1, and TMEM26, in cultured human visceral adipose-derived stem cells. In conclusion, BTM-0512 has stronger anti-obesity effect than resveratrol, which might be associated with activation of beige remodeling in subcutaneous adipose tissue.Recent studies revealed that sirtuin 1 （SIRT1） is involved in the regulation of energy metabolism and its agonist resveratrol showed anti-obesity effect. This study aims to determine whether BTM- 0512, a novel derivative of resveratrol, acts as an antagonist of obesity and to explore its possible mechanisms. High-fat diet （HFD）-induced obese mice were intragastrically administered with BTM-0512 （5, 10, and 20 mg/kg/day） or resveratrol （10mg/kg/day）. It was found that the body weight, Lee＇s index, ratio of visceral adipose tissue （VAT） to body weight, and blood glucose were significantly reduced in BTM-0512-treated mice when compared with those in mice treated with resveratrol. BTM-0512 up-regulated the expressions of SIRT1, full length PRDM16 （fPRDM16）, total PRDM16 （tPRDM16, including fPPRDM16 and other PRDM16 isoforms）, and uncoupling protein 1 （UCP1） in both brown and subcutaneous adipose tissues. Although BTM-0512 and resveratrol also up-regulated SIRT1 and tPRDM16 levels in VAT of HFD-induced obese mice, the expressions of fPRDM16, UCP1, and TMEM26 were down-regulated. In mouse primary subcutaneous preadipo- cytes cultured with or without adipogenic medium, BTM-0512 up-regulated fPRDM16, tPRDM16, and UCP1 expressions, which was reversed by SIRT1 antagonists. But in cultured brown and visceral adipocytes, the UCP1 protein level showed no significant change after treatment with 1 μM of BTM-0512. Moreover, transfection with human SIRT1 plasmid reduced lipid deposit, as well as the mRNA levels of fPRDM16, UCP1, and TMEM26, in cultured human visceral adipose-derived stem cells. In conclusion, BTM-0512 has stronger anti-obesity effect than resveratrol, which might be associated with activation of beige remodeling in subcutaneous adipose tissue.

关 键 词：BTM-0512 SIRT1 PRDM16 beige remodeling OBESITY 

分 类 号：Q[生物学]