title: Rutin ameliorates obesity through brown fat activation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: You
authors.affiliation: 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.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hyuek Jong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Meng
authors.initials: M
authors.lastname: Dong
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hanlin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Huiqiao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Ye
authors.affiliation: The University of the Chinese Academy of Sciences, Beijing, China.|State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Qi
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
authors.forename: Baiqiang
authors.initials: B
authors.lastname: Zhai
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Huang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Shunai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Zhoukou Normal University, Henan, China; and.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji, China.
authors.forename: Chengbi
authors.initials: C
authors.lastname: Cui
authors.affiliation: Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji, China.
authors.forename: Donghao
authors.initials: D
authors.lastname: Li
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: The University of the Chinese Academy of Sciences, Beijing, China; zqyuan@ibp.ac.cn.|State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; jinw@ioz.ac.cn.
authors.forename: Wanzhu
authors.initials: W
authors.lastname: Jin
mesh_terms: D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005951:Glucose Tolerance Test; D057809:HEK293 Cells; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D012431:Rutin / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C081930:Tfam protein, mouse; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D012431:Rutin; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: brown adipose tissue; energy expenditure; mitochondria; obesity; rutin