Journal
HEPATOLOGY RESEARCH
Volume 39, Issue 6, Pages 601-608Publisher
WILEY
DOI: 10.1111/j.1872-034X.2008.00485.x
Keywords
resveratrol; free fatty acids; profibrogenic activation
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Funding
- Deutsche Forschungsgemeinschaft CA [267/4-1]
- Wilhelm Laupitz Foundation
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To ascertain whether resveratrol affects the expression of free fatty acids (FFA)-induced profibrogenic genes, death receptors, and/or apoptosis-related molecules in human hepatic stellate cells, using the LX-2 cell line. Cells were cultured in the presence of FFAs (2:1 oleate : palmitate) and subsequently treated with resveratrol. Gene expression rates were determined by quantitative real-time PCR. The 50% lethal dose (LD50) of resveratrol in the presence of FFAs was assessed with the MTT viability test. Compared to vehicle controls, incubation of LX-2 cells with 0.5 mM FFAs induced profibrogenic genes (alpha-SMA x 2.9; TGF-beta 1 x 1.6; TIMP-1 x 1.4), death receptors (CD95/Fas x 3.8; TNFR-1 x 1.4), and anti-apoptotic molecules (Bcl-2 x 2.3; Mcl-1 x 1.3). Subsequent addition of 15 mu M resveratrol (LD50 = 23.2 mu M) significantly (P < 0.05) upregulated further these genes (alpha-SMA x 6.5; TGF-beta 1 x 1.9; TIMP-1 x 2.2; CD95/Fas x 13.1, TNFR-1 x 2.1; Bcl-2 x 3.6; Mcl-1 x 1.9). Importantly, this effect was only observed in the presence of FFAs. Resveratrol amplifies the profibrogenic activation of human hepatic LX-2 stellate cells. This finding raises the possibility that in obese patients with elevated FFAs reserveratrol could provoke hepatic fibrogenesis. In-vivo studies are necessary to further validate this conclusion.
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