Class III Alcohol Dehydrogenase Plays a Key Role in the Onset of Alcohol-Related/-Associated Liver Disease as an S-Nitrosoglutathione Reductase in Mice

Lipid accumulation in the liver due to chronic alcohol consumption (CAC) is crucial development of disease (ALD). It promoted by NADH/NAD ratio increase via dehydrogenase (ADH)-dependent metabolism and lipogenesis peroxisome proliferator-activated receptor γ (PPARγ) liver. The transcriptional activity PPARγ on lipogenic genes inhibited S-nitrosylation but activated denitrosylation S-nitrosoglutathione reductase (GSNOR), an enzyme identical ADH3. Besides ADH1, ADH3 also participates metabolism. Therefore, we investigated specific contribution ALD onset. ADH3-knockout (Adh3-/-) wild-type (WT) mice were administered a 10% ethanol solution for 12 months. Adh3-/- exhibited no significant pathological changes liver, whereas WT marked hepatic lipid (p < 0.005) with increased serum transaminase levels. death during CAC, 40% death. Liver mRNA levels elevated CAC 0.01). elimination rate measured after injecting 4 g/kg was not significantly different between two strains, although both strains CAC. Thus, plays key role onset, likely acting as GSNOR.