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Open Access Research article

Inhibitory effects of grape skin extract and resveratrol on fatty acid synthase

Yan Liang12, Weixi Tian1 and Xiaofeng Ma1*

Author Affiliations

1 College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China

2 School of Kinesiology and Health, Capital University of Physical Education and Sports, No. 11 Beisanhuanxi Road, Beijing 100191, China

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BMC Complementary and Alternative Medicine 2013, 13:361  doi:10.1186/1472-6882-13-361

Published: 16 December 2013



Grape skin, a rich source of phytochemicals, has been reported to possess remarkable anti-obesity activity. Fatty acid synthase (FAS) is a key enzyme catalyzing the synthesis of fatty acid de novo, and has been considered as an anti-obesity target. To elucidate the anti-obesity mechanism of grape skin, we investigated the effects of grape skin extract (GSE) and resveratrol, one of the phytochemicals in GSE, on FAS and FAS over-expressed 3 T3-L1 preadipocyte.


Purified FAS was obtained from chicken liver. Dried grape skin was extracted by 50% ethanol and partitioned by ethyl acetate. Inhibitory effects of GSE and resveratrol on FAS including fast-binding inhibition, time-dependent inhibition, and enzyme kinetics were determined. Inhibitory effects of GSE and resveratrol on 3T3-L1 preadipocyte were also measured.


GSE inhibited the overall reaction and β-ketoacyl reductase (KR) reaction of FAS with IC50 values of 4.61 μg/ml and 20.3 μg/ml. For inhibition by resveratrol, the relevant IC50 values were 11.1 μg/ml and 21.9 μg/ml, respectively. And both GSE and resveratrol showed time-dependent inhibition for FAS, with the kobs values of 0.028 min-1, and 0.040 min-1 respectively. They inhibited the overall reaction of FAS competitively with acetyl-CoA, noncompetitively with malonyl-CoA and in a mixed manner with NADPH. Moreover, the inhibition on KR domain by resveratrol was time-dependent with kobs value of 0.106 min-1. In 3 T3-L1 preadipocytes, resveratrol reduced lipid accumulation remarkably.


GSE and resveratrol are potent FAS inhibitors and they bound reversibly to the KR domain of FAS to inhibit the reduction of the saturated acyl groups in fatty acid synthesis. Based on the valid data and deliberate analysis, we proposed that GSE and resveratrol have great medical potential and officinal value in treating obesity and related diseases.

Fatty acid synthase; β-ketoacyl reductase; Inhibitor; Grape skin extract; Resveratrol; Obesity; 3 T3-L1 Preadipocytes