PLoS ONE (Jan 2013)

Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

  • Yiyi Sun,
  • Zhihe Zang,
  • Ling Zhong,
  • Min Wu,
  • Qing Su,
  • Xiurong Gao,
  • Wang Zan,
  • Dong Lin,
  • Yan Zhao,
  • Zhonglin Zhang

DOI
https://doi.org/10.1371/journal.pone.0063354
Journal volume & issue
Vol. 8, no. 5
p. e63354

Abstract

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Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.