Vol 49 No. 4: 318-327 [PDF] [Full Text]
Resveratrol derivative BTM-0512 mitigates obesity by promoting beige remodeling of subcutaneous preadipocytes
Qingqing Li1,†, Kuansong Wang2,3,†, Yipeng Ma1, Chunxiang Qin4, Changsheng Dong5, Ping Jin6, Yan Wu1, Xiaoming Xiong1, Niansheng Li1, Changping Hu1, Jun Peng1,7, and Zhichun Yang1,7,*

1Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China,
2Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China,
3Department of Pathology, School of Basic Medicine, Central South University, Changsha 410008, China,
4Department of Obstetrics and Gynecology, the Third Xiangya Hospital, Central South University, Changsha 410013, China,
5Division of Anesthetic, the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, China,
6Department of Endocrinology, the Third Xiangya Hospital, Central South University, Changsha 410013, China, and
7Hunan Provincial Key Laboratory of Cardiovascular Research, Changsha 410078, China
These authors contributed equally to this work.

Abstract  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 (10 mg/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 preadipocytes 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.


Keywords   BTM-0512, SIRT1, PRDM16, beige remodeling, obesity


Received   2016-11-3  


Funding  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).


* Correspondence address  Tel: +86-731-82355080; Fax: +86-731-82355078; E-mail: yzhichun@126.com

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