Low-dose trans-resveratrol induce poly(ADP)-ribosylation-dependent increase of the PPAR-γ protein expression level in the in vitro model of non-alcoholic fatty liver disease.

An effect of low-dose resveratrol treatment on lipid metabolism and pro-inflammatory processes has been studied, using an in vitro model of Non-Alcoholic-Fatty Liver Disease. The model system consisted of lipid-loaded monolayer cultures of hepatocytes (Hepa1-6) and macrophages (RAW264.7), as both cell types are present in the liver. Also a tridimensional model of hepatic spheroids has been created to mimic spatial adhesive contacts between cells. Treatment with resveratrol (5 μM, 10 μM) for 3 h caused a decrease in lipid load in all three model systems. This decrease wasn't accompanied by any changes in surface expression of lipid transporter-CD36. The response to resveratrol (RSV) was cell type- and cell environment-dependent. In both cell types an increase of the peroxisome proliferator-activated receptor-γ (PPAR-γ) protein level has been revealed. The increase of the PPAR-γ protein level appeared to be poly (ADP)-ribosylation-dependent. It has been revealed, that in the resveratrol-induced signaling pathway, leading to the decrease of intracellular lipid load, an activation of poly (ADP)-ribose polymerase should happen upstream of PPAR-γ protein expression.The decrease of lipid load isn't accompanied by changes in the surface expression of lipid transporter CD36.