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. 2017 Feb 28;26(1):263–269. doi: 10.1007/s10068-017-0035-0

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

Yeaji Park 1, Jeehye Sung 1, Jinwoo Yang 1, Hyeonmi Ham 2, Younghwa Kim 3, Heon-Sang Jeong 1, Junsoo Lee 1,✉
PMCID: PMC6049482  PMID: 30263537

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).

Keywords: esculetin, lipogenesis, AMPK, NAFLD, HepG2 cells

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