Pomegranate husk extract, punicalagin and ellagic acid inhibit fatty acid synthase and adipogenesis of 3T3-L1 adipocyte

Fatty acid synthase (FAS) has been recognized as a potential therapeutic target for obesity. In this study, for the first time, the inhibitory effect of pomegranate husk extract, punicalagin and ellagic acid on FAS was investigated. We found them potently inhibiting the activity of FAS with half-inhibitory concentration values (IC50) of 4.1 mu g/ml (pomegranate husk extract), 4.2 mu g/ml (4.50 mu M, punicalagin) and 1.31 mu g/ml (4.34 mu M, ellagic acid), respectively. Moreover, they all exhibited time-dependent inactivation of FAS. Punicalagin and ellagic acid inhibited FAS with different mechanisms compared to previously reported inhibitors, through inactivating acetyl/malonyl transferase and beta-ketoacyl synthase domains, respectively. Additionally, 100 mu g/ml pomegranate husk extract, 5.24 mu g/ml (5 mu M) punicalagin and 4.5 mu g/ml (15 mu M) ellagic acid effectively reduced lipid accumulation inside FAS over-expressed 3T3-L1 adipocytes. Since FAS plays a key role in the biosynthesis pathway of fatty acid, these findings suggest that pomegranate husk extract, punicalagin and ellagic acid have potential in the prevention and treatment of obesity. (C) 2013 Elsevier Ltd. All rights reserved.