Resveratrol derivative BTM-0512 mitigates obesity by promoting beige remodeling of subcutaneous preadipocytes
Resveratrol derivative BTM-0512 mitigates obesity by promoting beige remodeling of subcutaneous preadipocytes
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白藜芦醇衍生物 BTM-0512 通过促进皮下前脂肪细胞的米色重塑来减轻肥胖
DOI：
10.1093/abbs/gmx009
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发表时间：
2017-04-01
影响因子：
3.7
通讯作者：
Yang, Zhichun
中科院分区：
文献类型：
--
作者：
Li, Qingqing;Wang, Kuansong;Yang, Zhichun
最近的研究表明，sirtuin 1(SIRT1)参与了能量代谢的调节，其激动剂白藜芦醇具有抗肥胖作用。本研究旨在确定白藜芦醇的新衍生物BTM-0512是否具有肥胖拮抗剂的作用，并探讨其可能的机制。给高脂饮食诱导的肥胖小鼠灌胃BTM-0512(5、10和20 mg/kg/d)或白藜芦醇(10 mg/kg/d)。结果表明，BTM-0512组小鼠体重、Lee‘s指数、内脏脂肪组织/体重比和血糖均显著低于白藜芦醇组。BTM-0512上调棕色和皮下脂肪组织中SIRT1、全长PRDM16(FPRDM16)、总PRDM16(tPRDM16，包括fPPRDM16和其他PRDM16亚型)和解偶联蛋白1(UCP1)的表达。虽然BTM-0512和白藜芦醇也能上调HFD诱导的肥胖小鼠VAT中SIRT1和tPRDM16的水平，但fPRDM16、UCP1和TMEM26的表达却下调。在原代培养的小鼠皮下前脂肪细胞中，无论有无成脂介质，BTM-0512上调了fPRDM16、tPRDM16和UCP1的表达，这一上调可被SIRT1拮抗剂逆转。而在培养的棕色和内脏脂肪细胞中，经1μM的BTM0512处理后，UCP1蛋白水平无明显变化。此外，转染人SIRT1质粒减少了培养的人内脏脂肪干细胞中的脂质沉积，以及fPRDM16、UCP1和TMEM26的mRNA水平。结论：BTM-0512具有比白藜芦醇更强的抗肥胖作用，这可能与其激活皮下脂肪组织的米色重塑有关。
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.