Polymethoxyselenoflavones exert anti-obesity effects through activation of lipolysis and brown adipocyte metabolism
| Autor: | Hyun Jung Kwon, Abhirup Saha, Minsu Kim, Yeonho Son, Woo Ram Yang, Jin Hyun Jeong, Je Kyung Seong, Yun Hee Lee, Young Suk Jung, Yoon Keun Cho, Sang Yeop Ahn |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Lipolysis Endocrinology Diabetes and Metabolism Medicine (miscellaneous) Adipose tissue 030209 endocrinology & metabolism Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo 3T3-L1 Cells Adipocyte Internal medicine Brown adipose tissue medicine Animals Obesity 030212 general & internal medicine Selenium Compounds Flavonoids Mice Knockout Nutrition and Dietetics Lipid metabolism Disease Models Animal Adipocytes Brown Endocrinology medicine.anatomical_structure chemistry Adipogenesis Knockout mouse Anti-Obesity Agents |
| Zdroj: | International Journal of Obesity. 45:122-129 |
| ISSN: | 1476-5497 0307-0565 |
| Popis: | 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. 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. 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. Collectively, our results indicated that DMPSC exerted anti-obesity effects partially through the PKA signaling-mediated activation of lipolysis and brown adipose tissue metabolism. |
| Databáze: | OpenAIRE |
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