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Resveratrol amplifies profibrogenic effects of free fatty acids on human hepatic stellate cells
Author(s) -
Bechmann Lars P.,
Zahn Denis,
Gieseler Robert K.,
Fingas Christian D.,
Marquitan Guido,
Jochum Christoph,
Gerken Guido,
Friedman Scott L.,
Canbay Ali
Publication year - 2009
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2008.00485.x
Subject(s) - resveratrol , hepatic stellate cell , apoptosis , receptor , fas receptor , downregulation and upregulation , microbiology and biotechnology , viability assay , in vitro , biology , chemistry , endocrinology , medicine , pharmacology , programmed cell death , gene , biochemistry
Aim: 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. Methods: 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 (LD 50 ) of resveratrol in the presence of FFAs was assessed with the MTT viability test. Results: Compared to vehicle controls, incubation of LX‐2 cells with 0.5 mM FFAs induced profibrogenic genes (α‐SMA × 2.9; TGF‐β1 × 1.6; TIMP‐1 × 1.4), death receptors (CD95/Fas × 3.8; TNFR‐1 × 1.4), and anti‐apoptotic molecules (Bcl‐2 × 2.3; Mcl‐1 × 1.3). Subsequent addition of 15 µM resveratrol (LD 50 = 23.2 µM) significantly ( P < 0.05) upregulated further these genes (α‐SMA × 6.5; TGF‐β1 × 1.9; TIMP‐1 × 2.2; CD95/Fas × 13.1, TNFR‐1 × 2.1; Bcl‐2 × 3.6; Mcl‐1 × 1.9). Importantly, this effect was only observed in the presence of FFAs. Conclusion: 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.