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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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).
Keywordsesculetin lipogenesis AMPK NAFLD HepG2 cells
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- 9.Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 13: 376–388 (2011)CrossRefGoogle Scholar
- 10.Shimano H, Yahagi N, Amemiya-Kudo M, Hasty AH, Osuga J, Tamura Y, Shionoiri F, Iizuka Y, Ohashi K, Harada K, Gotoda T, Ishibashi S, Yamada N. Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. J. Biol. Chem. 274: 35832–35839 (1999)CrossRefGoogle Scholar
- 11.Harvatine KJ, Bauman DE. SREBP1 and thyroid hormone responsive spot 14 (S14) are involved in the regulation of bovine mammary lipid synthesis during diet-induced milk fat depression and treatment with CLA. J. Nutr. 136: 2468–2474 (2006)Google Scholar
- 22.Paschos P, Paletas K. Non alcoholic fatty liver disease and metabolic syndrome. Hippokratia 13: 9–19 (2009)Google Scholar
- 29.Hwang YP, Choi JH, Han EH, Kim HG, Wee JH, Jung KO, Jung KH, Kwon KI, Jeong TC, Chung YC, Jeong HG. Purple sweet potato anthocyanins attenuate hepatic lipid accumulation through activating adenosine monophosphate-activated protein kinase in human HepG2 cells and obese mice. Nutr. Res. 31: 896–906 (2011)CrossRefGoogle Scholar