title: Resveratrol amplifies profibrogenic effects of free fatty acids on human hepatic stellate cells.
abstract: OBJECTIVE
  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 (alpha-SMA x 2.9; TGF-beta1 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 microM resveratrol (LD(50) = 23.2 microM) significantly (P < 0.05) upregulated further these genes (alpha-SMA x 6.5; TGF-beta1 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors.forename: Lars P
authors.initials: LP
authors.lastname: Bechmann
authors.forename: Denis
authors.initials: D
authors.lastname: Zahn
authors.forename: Robert K
authors.initials: RK
authors.lastname: Gieseler
authors.forename: Christian D
authors.initials: CD
authors.lastname: Fingas
authors.forename: Guido
authors.initials: G
authors.lastname: Marquitan
authors.forename: Christoph
authors.initials: C
authors.lastname: Jochum
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Scott L
authors.initials: SL
authors.lastname: Friedman
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay