title: Alcohol deranges hepatic lipid metabolism via altered transcriptional regulation.
abstract: Alcohol has classically been thought to cause fatty liver by way of altered redox potential in the liver, which inhibits fatty acid oxidation. Additional effects appear to play a role both in impairing fat oxidation and stimulating lipogenesis. Alcohol reduces the DNA binding and transcription-activating properties of peroxisome proliferator-activated receptor alpha (PPARalpha), both in cultured cells and in mice fed alcohol. Treatment of alcohol-fed mice with a PPARalpha agonist reverses fatty liver despite continued alcohol consumption. Alcohol also activates sterol response element- binding protein 1 (SREBP-1), inducing a battery of lipogenic enzymes. This effect may be due in part to inhibition of AMP-dependent protein kinase. This understanding of alcohol effects provides new therapeutic targets to reverse alcoholic fatty liver.
authors.affiliation: Department of Medicine, Indianapolis, Indiana, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Crabb
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D000431:Ethanol / Q000633:toxicity*; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D047493:PPAR alpha; D051780:Sterol Regulatory Element Binding Protein 1; D000431:Ethanol; D000263:Adenylate Kinase