Resveratrol derivative BTM-0512 mitigates obesity by promoting beige remodeling of subcutaneous preadipocytes.
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.
Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Qingqing
Q
Li
Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China.|Department of Pathology, School of Basic Medicine, Central South University, Changsha 410008, China.
Kuansong
K
Wang
Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Yipeng
Y
Ma
Department of Obstetrics and Gynecology, the Third Xiangya Hospital, Central South University, Changsha 410013, China.
Chunxiang
C
Qin
Division of Anesthetic, the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, China.
Changsheng
C
Dong
Department of Endocrinology, the Third Xiangya Hospital, Central South University, Changsha 410013, China.
Ping
P
Jin
Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Yan
Y
Wu
Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Xiaoming
X
Xiong
Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Niansheng
N
Li
Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Changping
C
Hu
Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.|Hunan Provincial Key Laboratory of Cardiovascular Research, Changsha 410078, China.
Jun
J
Peng
Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.|Hunan Provincial Key Laboratory of Cardiovascular Research, Changsha 410078, China.
Zhichun
Z
Yang
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000069796:Adipose Tissue, Beige / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism
C497286:3,4',5-trimethoxystilbene; D004268:DNA-Binding Proteins; C416371:PRDM16 protein, human; C521133:Prdm16 protein, mouse; D013267:Stilbenes; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; D056564:Sirtuin 1; D000077185:Resveratrol
BTM-0512; PRDM16; SIRT1; beige remodeling; obesity