Inhibitory effect of esculetin on free-fatty-acid-induced lipid accumulation in human HepG2 cells through activation of AMP-activated protein kinase

This study aimed to determine the lipid-lowering effect of esculetin (6,7-dihydroxycoumarin), a coumarin derivative, using a cell model of steatosis induced by a mixture of free fatty acids (FFAs). Esculetin dose-dependently inhibited intracellular lipid accumulation by down-regulating the protein e...

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Published in	Food Science and Biotechnology Vol. 26; no. 1; pp. 263 - 269
Main Authors	Park, Yeaji, Sung, Jeehye, Yang, Jinwoo, Ham, Hyeonmi, Kim, Younghwa, Jeong, Heon-Sang, Lee, Junsoo
Format	Journal Article
Language	English
Published	Seoul Springer Science and Business Media LLC 01.02.2017 The Korean Society of Food Science and Technology Springer Nature B.V 한국식품과학회
Subjects	Accumulation Adenosine monophosphate AMP-activated protein kinase Bioaccumulation Chemistry Chemistry and Materials Science Coumarin Fatty acids fatty liver fatty-acid synthase Food Science free fatty acids genes hepatocytes human cell lines humans Kinases lipemic effect Lipids lipogenesis Nutrition protein synthesis Proteins signal transduction sterols 식품과학 esculetin AMPK NAFLD lipogenesis HepG2 cells
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ISSN	1226-7708 2092-6456 2092-6456
DOI	10.1007/s10068-017-0035-0

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Abstract	This study aimed to determine the lipid-lowering effect of esculetin (6,7-dihydroxycoumarin), a coumarin derivative, using a cell model of steatosis induced by a mixture of free fatty acids (FFAs). Esculetin dose-dependently inhibited intracellular lipid accumulation by down-regulating the protein expression of lipogenic genes such as sterol regulatory element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS) in FFAs-induced HepG2 cells. Moreover, esculetin significantly elevated the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathways in HepG2 hepatocytes. The anti-lipogenic effects of esculetin mediated by AMPK activation were abolished when FFAs-induced HepG2 cells were treated with a specific inhibitor of AMPK, i.e., compound C. These results suggest that esculetin attenuates hepatic lipid accumulation by inhibiting lipogenesis through the modulation of AMPK signaling pathway on FFAs-induced steatosis in HepG2 cells and may be used for the prevention of nonalcoholic fatty liver disease (NAFLD).
AbstractList	This study aimed to determine the lipid-lowering effect of esculetin (6,7-dihydroxycoumarin), a coumarin derivative, using a cell model of steatosis induced by a mixture of free fatty acids (FFAs). Esculetin dose-dependently inhibited intracellular lipid accumulation by down-regulating the protein expression of lipogenic genes such as sterol regulatory element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS) in FFAs-induced HepG2 cells. Moreover, esculetin significantly elevated the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathways in HepG2 hepatocytes. The anti-lipogenic effects of esculetin mediated by AMPK activation were abolished when FFAs-induced HepG2 cells were treated with a specific inhibitor of AMPK, i.e., compound C. These results suggest that esculetin attenuates hepatic lipid accumulation by inhibiting lipogenesis through the modulation of AMPK signaling pathway on FFAs-induced steatosis in HepG2 cells and may be used for the prevention of nonalcoholic fatty liver disease (NAFLD).This study aimed to determine the lipid-lowering effect of esculetin (6,7-dihydroxycoumarin), a coumarin derivative, using a cell model of steatosis induced by a mixture of free fatty acids (FFAs). Esculetin dose-dependently inhibited intracellular lipid accumulation by down-regulating the protein expression of lipogenic genes such as sterol regulatory element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS) in FFAs-induced HepG2 cells. Moreover, esculetin significantly elevated the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathways in HepG2 hepatocytes. The anti-lipogenic effects of esculetin mediated by AMPK activation were abolished when FFAs-induced HepG2 cells were treated with a specific inhibitor of AMPK, i.e., compound C. These results suggest that esculetin attenuates hepatic lipid accumulation by inhibiting lipogenesis through the modulation of AMPK signaling pathway on FFAs-induced steatosis in HepG2 cells and may be used for the prevention of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the lipid-lowering effect of esculetin (6,7-dihydroxycoumarin), a coumarin derivative, using a cell model of steatosis induced by a mixture of free fatty acids (FFAs). Esculetin dose-dependently inhibited intracellular lipid accumulation by down-regulating the protein expression of lipogenic genes such as sterol regulatory element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS) in FFAs-induced HepG2 cells. Moreover, esculetin significantly elevated the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathways in HepG2 hepatocytes. The anti-lipogenic effects of esculetin mediated by AMPK activation were abolished when FFAs-induced HepG2 cells were treated with a specific inhibitor of AMPK, i.e., compound C. These results suggest that esculetin attenuates hepatic lipid accumulation by inhibiting lipogenesis through the modulation of AMPK signaling pathway on FFAs-induced steatosis in HepG2 cells and may be used for the prevention of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the lipid-lowering effect of esculetin (6,7-dihydroxycoumarin), a coumarin derivative, using a cell model of steatosis induced by a mixture of free fatty acids (FFAs). Esculetin dose-dependently inhibited intracellular lipid accumulation by down-regulating the protein expression of lipogenic genes such as sterol regulatory element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS) in FFAs-induced HepG2 cells. Moreover, esculetin significantly elevated the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathways in HepG2 hepatocytes. The anti-lipogenic effects of esculetin mediated by AMPK activation were abolished when FFAs-induced HepG2 cells were treated with a specific inhibitor of AMPK, i.e., compound C. These results suggest that esculetin attenuates hepatic lipid accumulation by inhibiting lipogenesis through the modulation of AMPK signaling pathway on FFAs-induced steatosis in HepG2 cells and may be used for the prevention of nonalcoholic fatty liver disease (NAFLD). KCI Citation Count: 9
Author	Jinwoo Yang Yeaji Park Jeehye Sung Younghwa Kim Heon-Sang Jeong Junsoo Lee Hyeonmi Ham
Author_xml	– sequence: 1 givenname: Yeaji surname: Park fullname: Park, Yeaji organization: Division of Food and Animal Sciences, Chungbuk National University – sequence: 2 givenname: Jeehye surname: Sung fullname: Sung, Jeehye organization: Division of Food and Animal Sciences, Chungbuk National University – sequence: 3 givenname: Jinwoo surname: Yang fullname: Yang, Jinwoo organization: Division of Food and Animal Sciences, Chungbuk National University – sequence: 4 givenname: Hyeonmi surname: Ham fullname: Ham, Hyeonmi organization: Department of Central Area, National Institute of Crop Science, Rural Development Administration – sequence: 5 givenname: Younghwa surname: Kim fullname: Kim, Younghwa organization: School of Food Biotechnology and Nutrition, Kyungsung University – sequence: 6 givenname: Heon-Sang surname: Jeong fullname: Jeong, Heon-Sang organization: Division of Food and Animal Sciences, Chungbuk National University – sequence: 7 givenname: Junsoo surname: Lee fullname: Lee, Junsoo email: junsoo@chungbuk.ac.kr organization: Division of Food and Animal Sciences, Chungbuk National University
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SubjectTerms	Accumulation Adenosine monophosphate AMP-activated protein kinase Bioaccumulation Chemistry Chemistry and Materials Science Coumarin Fatty acids fatty liver fatty-acid synthase Food Science free fatty acids genes hepatocytes human cell lines humans Kinases lipemic effect Lipids lipogenesis Nutrition protein synthesis Proteins signal transduction sterols 식품과학
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Title	Inhibitory effect of esculetin on free-fatty-acid-induced lipid accumulation in human HepG2 cells through activation of AMP-activated protein kinase
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