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.
Bibliographical noteFunding Information:
This research was supported by Basic Science Research Program [ NRF-2019R1C1C1002014 (Y.H.L) NRF-2018R1A5A2024425 ] of Ministry of Science of ICT and by Korea Mouse Phenotyping Project [ NRF-2013M3A9D5072550 , NRF-2016M3A9D5A01953818 ] of Ministry of Science of ICT and Future Planning through National Research Foundation of Korea (NRF). This work was performed within the program of the AMOREPACIFIC Open Research [ ORT-01-R19E999009 ] supported by a grant from AMOREPACIFIC .
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Molecular Biology
- Nutrition and Dietetics
- Clinical Biochemistry