Yuan Xiaoxue, Wei Gang, You Yilin, Huang Yuanyuan, Lee Hyuek Jong, Dong Meng, Lin Jun, Hu Tao, Zhang Hanlin, Zhang Chuanhai, Zhou Huiqiao, Ye Rongcai, Qi Xiaolong, Zhai Baiqiang, Huang Weidong, Liu Shunai, Xie Wen, Liu Qingsong, Liu Xiaomeng, Cui Chengbi, Li Donghao, Zhan Jicheng, Cheng Jun, Yuan Zengqiang, Jin Wanzhu
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
The University of the Chinese Academy of Sciences, Beijing, China.
FASEB J. 2017 Jan;31(1):333-345. doi: 10.1096/fj.201600459RR. Epub 2016 Oct 20.
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 from mulberry and a drug used as a capillary stabilizer clinically for many years without any side effects, regulated whole-body energy metabolism 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.
通过激活棕色脂肪组织(BAT)增加能量消耗是治疗肥胖症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,作为一种毛细血管稳定剂在临床上使用多年且无任何副作用,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棕色样脂肪细胞(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共激活因子-1α蛋白的低乙酰化,从而刺激线粒体转录因子A(Tfam)的反式激活,并最终增加BAT中的线粒体数量和解偶联蛋白1(UCP1)活性。这些发现表明芦丁是一种激活BAT的新型小分子,可能为治疗代谢紊乱提供一种新的治疗方法。-袁,X.,魏,G.,尤,Y.,黄,Y.,李,H.J.,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症