Rutin ameliorates obesity through brown fat activation

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.

Keywords: brown adipose tissue; energy expenditure; mitochondria; obesity; rutin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / physiology*
  • Animals
  • Body Temperature Regulation / drug effects
  • Body Temperature Regulation / physiology
  • Cold Temperature
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Diet, High-Fat / adverse effects*
  • Energy Metabolism / drug effects*
  • Glucose Tolerance Test
  • HEK293 Cells
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism
  • Humans
  • Mice
  • Mice, Obese
  • Obesity / drug therapy*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Rutin / pharmacology*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism


  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Tfam protein, mouse
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Rutin
  • Sirt1 protein, mouse
  • Sirtuin 1