Polymethoxyselenoflavones exert anti-obesity effects through activation of lipolysis and brown adipocyte metabolism

Hyun Jung Kwon, Abhirup Saha, Sang Yeop Ahn, Yoon Keun Cho, Yeonho Son, Minsu Kim, Je Kyung Seong, Woo Ram Yang, Young Suk Jung, Jin Hyun Jeong, Yun Hee Lee

Research output: Contribution to journalArticle

Abstract

Background/objectives: Polymethoxyselenoflavone (PMSF) is a compound that substitutes the oxygen atom in a flavonoid with selenium. This study aimed to investigate the effects of PMSFs on lipid metabolism in adipocytes and their anti-obesity potential. Subjects/methods: To test lipolytic and thermogenic effects of the compounds in vitro, adipocytes differentiated from immortalized pre-brown adipocyte progenitors and pre-white adipocyte cell lines were treated with 19 PMSFs. The expression levels of brown adipocyte markers and genes related to mitochondrial metabolism were analyzed by qPCR and western blot. In vivo anti-obesity effect was investigated using diet-induced obesity mouse models and adipocyte-specific ATGL knockout mice. Results: The qPCR analysis identified 2-(3,4-dimethoxyphenyl)-4H-selenochromen-4-one (DMPSC) as the most potent brown adipogenic candidate among the 19 compounds tested in this study. DMPSC treatment significantly increased the mitochondrial content and oxidative metabolism in adipocytes in vitro. Mechanistically, DMPSC treatment increased lipolysis through activation of PKA downstream signaling. Consistently, the in vivo treatment of DMPSC increased energy consumption, reduced body weight, and improved glucose tolerance in mice fed with high-fat diets. Moreover, DMPSC treatment increased brown adipocyte marker expression and mitochondrial content in adipose tissue of mice. The anti-obesity effects were absent in adipocyte-specific ATGL knockout mice, indicating that the DMPSC effect is mediated by cytosolic lipase-dependent mechanisms. Conclusions: Collectively, our results indicated that DMPSC exerted anti-obesity effects partially through the PKA signaling-mediated activation of lipolysis and brown adipose tissue metabolism.

Original languageEnglish
JournalInternational Journal of Obesity
DOIs
Publication statusAccepted/In press - 2020

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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    Kwon, H. J., Saha, A., Ahn, S. Y., Cho, Y. K., Son, Y., Kim, M., Seong, J. K., Yang, W. R., Jung, Y. S., Jeong, J. H., & Lee, Y. H. (Accepted/In press). Polymethoxyselenoflavones exert anti-obesity effects through activation of lipolysis and brown adipocyte metabolism. International Journal of Obesity. https://doi.org/10.1038/s41366-020-0606-7