1. Resveratrol derivative BTM-0512 mitigates obesity by promoting beige remodeling of subcutaneous preadipocytes
- Author
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Zhi-Chun Yang, Kuansong Wang, Changsheng Dong, Yan Wu, Xiao-Ming Xiong, Ping Jin, Jun Peng, Yipeng Ma, Nian-Sheng Li, Chang-Ping Hu, Qingqing Li, and Chunxiang Qin
- Subjects
Male ,0301 basic medicine ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Blotting, Western ,Subcutaneous Fat ,Biophysics ,Gene Expression ,Adipose tissue ,Resveratrol ,Biology ,Diet, High-Fat ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Adipose Tissue, Brown ,Sirtuin 1 ,Internal medicine ,Stilbenes ,Adipocytes ,medicine ,Animals ,Humans ,Obesity ,Cells, Cultured ,Uncoupling Protein 1 ,PRDM16 ,Molecular Structure ,Reverse Transcriptase Polymerase Chain Reaction ,Body Weight ,General Medicine ,Adipose Tissue, Beige ,Thermogenin ,DNA-Binding Proteins ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,chemistry ,Adipogenesis ,030220 oncology & carcinogenesis ,biology.protein ,Stem cell ,Transcription Factors - 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.
- Published
- 2017
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