Antiobesity effects of coumestrol through expansion and activation of brown adipose tissue metabolism

Sang Nam Kim, Sang Yeop Ahn, Hyun Doo Song, Hyun Jung Kwon, Abhirup Saha, Yeonho Son, Yoon Keun Cho, Young Suk Jung, Hyun Woo Jeong, Yun Hee Lee

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Abstract

Coumestrol is a dietary phytoestrogen with estrogen-mimicking characteristics. This study investigated the molecular mechanisms of antiobesity effects of coumestrol. Two weeks of coumestrol treatment reduced body weight and improved glucose tolerance of high-fat diet (HFD)-fed mice. Notably, coumestrol treatment reduced adiposity but expanded brown adipose tissue mass. In addition, coumestrol treatment induced up-regulation of brown adipocyte markers and lipolytic gene expression in adipose tissue. Mechanistically, coumestrol induced an increase in mitochondrial contents of brown adipose tissue, which was associated with up-regulation of adenosine monophosphate-activated protein kinase and sirtuin 1. In vitro knockdown of estrogen receptor 1 inhibited the effect of coumestrol on brown adipogenic marker expression, increase in mitochondrial contents and oxygen consumption rate in brown adipocytes. Furthermore, lineage tracing of platelet-derived growth factor receptor A-positive (PDGFRA+) adipocyte progenitors confirmed increased levels of de novo brown adipogenesis from PDGFRA+ cells by coumestrol treatment. In conclusion, our results indicate that coumestrol has antiobesity effects through the expansion and activation of brown adipose tissue metabolism.

Original languageEnglish
Article number108300
JournalJournal of Nutritional Biochemistry
Volume76
DOIs
Publication statusPublished - 2020 Feb

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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    Kim, S. N., Ahn, S. Y., Song, H. D., Kwon, H. J., Saha, A., Son, Y., Cho, Y. K., Jung, Y. S., Jeong, H. W., & Lee, Y. H. (2020). Antiobesity effects of coumestrol through expansion and activation of brown adipose tissue metabolism. Journal of Nutritional Biochemistry, 76, [108300]. https://doi.org/10.1016/j.jnutbio.2019.108300