Effects of binge ethanol on lipid homeostasis and oxidative stress in a rat model of nonalcoholic fatty liver disease.
Excess fat accumulation renders the liver more vulnerable to ethanol, but it is still unclear how alcohol enhances lipid dysmetabolism and oxidative stress in a pre-existing steatosis condition. The effects produced by binge ethanol consumption in the liver of male Wistar rats fed a standard (Ctrl) or a high-fat diet HFD were compared. The liver status was checked through tissue histology and standard serum parameters. Alteration of hepatic lipid homeostasis and consequent oxidative unbalance were assessed by quantifying the mRNA expression of the lipid-regulated peroxisome proliferator-activated receptors (PPARs), of the cytochromes CYP2E1 and CYP4A1, and of some antioxidant molecules such as the metallothionein isoforms MT1 and MT2 and the enzymes catalase and superoxide dismutase. The number of adipose differentiation-related protein (ADRP)-positive lipid droplets (LDs) was evaluated by immunohistochemical staining. As a response to the double insult of diet and ethanol the rat liver showed: (1) a larger increase in fat accumulation within ADRP-positive LDs; (2) stimulation of lipid oxidation in the attempt to limit excess fat accumulation; (3) induction of antioxidant proteins (MT2, in particular) to protect the liver from the ethanol-induced overproduction of oxygen radicals. The data indicate an increased susceptibility of fatty liver to ethanol and suggest that the synergistic effect of diet and ethanol on lipid dysmetabolism might be mediated, at least in part, by PPARs and cytochromes CYP4A1 and CYP2E1.
Dipartimento di Scienze della Terra, dell'Ambiente e della Vita (DISTAV), Università di Genova, Corso Europa 26, 16132, Genoa, Italy.
Elena
E
Grasselli
Adriana
A
Voci
Ilaria
I
Demori
Rita
R
De Matteis
Andrea D
AD
Compalati
Gabriella
G
Gallo
Laura
L
Vergani
D000818:Animals; D001483:Base Sequence; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D042926:Cytochrome P-450 CYP4A / Q000378:metabolism; D017931:DNA Primers; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects*; D050356:Lipid Metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
D017931:DNA Primers; D047492:Peroxisome Proliferator-Activated Receptors; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D042926:Cytochrome P-450 CYP4A