4.6 Article

The natural compound rutaecarpine promotes white adipocyte browning through activation of the AMPK-PRDM16 axis

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.01.080

Keywords

White adipocyte; Beige adipocyte; Browning; Rutaecarpine; AMPK

Funding

  1. Frontier Research Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) [2018GZR110105019]
  2. Guangzhou International Collaborative Grant [2019A050510027]
  3. International Partnership Program of the Chinese Academy of Sciences [154144KYSB20180063]
  4. National Natural Science Foundation of China [81,970,729, 81,874,322, 81,670,800]
  5. National Key R&D Program of China, Synthetic Biology Research [2019YFA0904500]
  6. Science and Technology Planning Project of Guangdong Province, China [2020B1212060052]
  7. Guangdong Provincial Public Interest Research and Capacity Building Projects [2014A010107024]
  8. Natural Science Foundation of Jiangsu Province, China [BK20171331]

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Rutaecarpine, a small molecule, induces adipocyte browning and regulates the AMPK signaling pathway, presenting a potential drug candidate for obesity treatment.
The prevalence of obesity is increasing globally and is associated with many metabolic disorders, such as type 2 diabetes and cardiovascular diseases. In recent years, a number of studies suggest that promotion of white adipose browning represents a promising strategy to combat obesity and its related metabolic disorders. The aim of this study was to identify compounds that induce adipocyte browning and elucidate their mechanism of action. Among the 500 natural compounds screened, a small molecule named Rutaecarpine, was identified as a positive regulator of adipocyte browning both in vitro and in vivo. KEGG pathway analysis from RNA-seq data suggested that the AMPK signaling pathway was regulated by Rutaecarpine, which was validated by Western blot analysis. Furthermore, inhibition of AMPK signaling mitigated the browning effect of Rutaecaripine. The effect of Rutaecaripine on adipocyte browning was also abolished upon deletion of Prdm16, a downstream target of AMPK pathway. In collusion, Rutaecarpine is a potent chemical agent to induce adipocyte browning and may serve as a potential drug candidate to treat obesity. (c) 2021 Elsevier Inc. All rights reserved.

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