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

• 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
• ISSN: 1226-7708; 2092-6456; 2092-6456
• DOI: 10.1007/s10068-017-0035-0

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).