Alcohol and lipid metabolism.
Hepatic lipid metabolism is controlled by several master transcription factors, in particular peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and sterol response element binding protein-1 (SREBP-1). Peroxisome proliferator-activated receptor-alpha is a receptor for free fatty acids (FFA), and can activate genes involved in transport, oxidation, and export of FFA. Sterol response element binding protein-1 is a sensor for the level of cholesterol in the liver, and is able to activate genes involved in synthesis of cholesterol and FFA. Chronic ethanol treatment of cells or animals inhibited PPAR-alpha function and activated SREBP. In addition, ethanol inhibited adenosine monophosphate-dependent protein kinase (AMPK). The AMPK controls fatty acid metabolism by inhibiting acetyl-coenzyme A carboxylase, reducing malonyl-coenzyme A, and thereby permitting fatty acid transport into and oxidation in the mitochondrion. Adenosine monophosphate-dependent protein kinase was inhibited in alcohol-treated animals and cells. The mechanisms by which ethanol affects AMPK and the transcription factors are as yet incompletely understood.
Crabb
David W
DW
Indiana Alcohol Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, USA. dcrabb@iupui.edu
Liangpunsakul
Suthat
S
D055372:AMP-Activated Protein Kinases; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005235:Fatty Liver, Alcoholic / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism*; D020025:Peroxisome Proliferators; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*
D009097:Multienzyme Complexes; D047493:PPAR alpha; D020025:Peroxisome Proliferators; D051780:Sterol Regulatory Element Binding Protein 1; D000431:Ethanol; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases