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Polymethoxyselenoflavones exert anti-obesity effects through activation of lipolysis and brown adipocyte metabolism.
Kwon, Hyun-Jung; Saha, Abhirup; Ahn, Sang-Yeop; Cho, Yoon Keun; Son, Yeonho; Kim, Minsu; Seong, Je Kyung; Yang, Woo-Ram; Jung, Young-Suk; Jeong, Jin-Hyun; Lee, Yun-Hee.
Afiliação
  • Kwon HJ; College of Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea.
  • Saha A; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
  • Ahn SY; College of Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea.
  • Cho YK; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
  • Son Y; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
  • Kim M; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
  • Seong JK; Korea Mouse Phenotyping Center (KMPC) and College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.
  • Yang WR; College of Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea.
  • Jung YS; College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea.
  • Jeong JH; College of Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea.
  • Lee YH; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea. yunhee.lee@snu.ac.kr.
Int J Obes (Lond) ; 45(1): 122-129, 2021 01.
Article em En | MEDLINE | ID: mdl-32467614
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Flavonoides / Compostos de Selênio / Fármacos Antiobesidade / Adipócitos Marrons / Lipólise Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Flavonoides / Compostos de Selênio / Fármacos Antiobesidade / Adipócitos Marrons / Lipólise Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article