Rutin ameliorates obesity through brown fat activation
Rutin ameliorates obesity through brown fat activation
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芦丁通过激活棕色脂肪改善肥胖
DOI：
10.1096/fj.201600459rr
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发表时间：
2017-01-01
期刊：
影响因子：
4.8
通讯作者：
Jin, Wanzhu
中科院分区：
文献类型：
--
作者：
Yuan, Xiaoxue;Wei, Gang;Jin, Wanzhu
通过激活棕色脂肪组织（BAT）增加能量消耗是治疗肥胖和糖尿病的关键方法。在本研究中，芦丁是一种从桑树中提取的天然化合物，也是一种临床上多年用作毛细血管稳定剂且无任何副作用的药物，它通过增强BAT活性来调节全身能量代谢。芦丁治疗显著降低了遗传性肥胖（Db/Db）和饮食诱导肥胖（DIO）小鼠的肥胖程度，增加了能量消耗，并改善了葡萄糖稳态。芦丁还在两种肥胖小鼠模型的皮下脂肪组织中诱导了类棕色脂肪细胞（米色脂肪细胞）的形成。从机制上讲，我们发现芦丁直接结合并稳定SIRT1，导致过氧化物酶体增殖物激活受体γ辅激活因子 - 1α蛋白的低乙酰化，从而刺激Tfam反式激活，并最终增加BAT中的线粒体数量和UCP1活性。这些发现表明，芦丁是一种激活BAT的新型小分子，可能为代谢紊乱的治疗提供一种新的治疗方法。 - 袁X，魏G，游Y，黄Y，李HJ，董M，林J，胡T，张H，张C，周H，叶R，齐X，翟B，黄W，刘S，谢W，刘Q，刘X，崔C，李D，詹J，程J，袁Z，金W。芦丁通过激活棕色脂肪改善肥胖。
Increasing energy expenditure through activation of brown adipose tissue (BAT) is a critical approach to treating obesity and diabetes. In this study, rutin, a natural compound extracted frommulberry and a drug used as a capillary stabilizer clinically formany years without any side effects, regulated whole‐body energymetabolism by enhancing BAT activity. Rutin treatment significantly reduced adiposity, increased energy expenditure, and improved glucose homeostasis in both genetically obese (Db/Db) and diet‐induced obesity (DIO) mice. Rutin also induced brown‐like adipocyte (beige) formation in subcutaneous adipose tissue in both obesity mouse models. Mechanistically, we found that rutin directly bound to and stabilized SIRT1, leading to hypoacetylation of peroxisome proliferator‐activated receptor γ coactivator‐1α protein, which stimulated Tfam transactivation and eventually augmented the number of mitochondria and UCP1 activity in BAT. These findings reveal that rutin is a novel small molecule that activates BAT and may provide a novel therapeutic approach to the treatment of metabolic disorders.—Yuan, X., Wei, G., You, Y., Huang, Y., Lee, H. J., Dong, M., Lin, J., Hu, T., Zhang, H., Zhang, C., Zhou, H., Ye, R., Qi, X., Zhai, B., Huang, W., Liu, S., Xie, W., Liu, Q., Liu, X., Cui, C., Li, D., Zhan, J., Cheng, J., Yuan, Z., Jin, W. Rutin ameliorates obesity through brown fat activation. FASEB J. 31, 333–345 (2017) www.fasebj.org