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 (LD50) 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 (LD50 = 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.