Resveratrol amplifies profibrogenic effects of free fatty acids on human hepatic stellate cells

    loading  Checking for direct PDF access through Ovid



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 (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.


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.

Related Topics

    loading  Loading Related Articles