Recent Developments in Alcoholism

Volume 14 of the series Recent Developments in Alcoholism pp 97-134

Alcohol and Lipids

  • Enrique BaraonaAffiliated withDepartment of Medicine, Mount Sinai School of MedicineBronx VA Medical Center
  • , Charles S. LieberAffiliated withDepartments of Medicine and Pathology, Mount Sinai School of MedicineAlcohol Dependence Treatment Program and Section of Liver Disease and Nutrition, Bronx VA Medical Center

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Alcoholic fatty liver and hyperlipemia result from the interaction of ethanol and its oxidation products with hepatic lipid metabolism. An early target of ethanol toxicity is mito-chondrial fatty acid oxidation. Acetaldehyde and reactive oxygen species have been incriminated in the pathogenesis of the mitochondrial injury. Microsomal changes offset deleterious accumulation of fatty acids, leading to enhanced formation of triacylglycerols, which are partly secreted into the plasma and partly accumulate in the liver. However, this compensatory mechanism fades with progression of the liver injury, whereas the production of toxic metabolites increases, exacerbating the lesions and promoting fibrogenesis. The early presence of these changes confers to the fatty liver a worse prognosis than previously thought. Alcoholic hyperlipemia results primarily from increased hepatic secretion of very-low-density lipoprotein and secondarily from impairment in the removal of triacylglycerol-rich lipoproteins from the plasma . Hyperlipemia tends to disappear because of enhanced lipolytic activity and aggravation of the liver injury. With moderate alcohol consumption, the increase in high-density lipoprotein becomes the predominant feature. Its mechanism is multifactorial (increased hepatic secretion and increased extra-hepatic formation as well as decreased removal) and explains part of the enhanced cholesterol transport from tissues to bile. These changes contribute to, but do not fully account for, the effects on atherosclerosis and/or coronary heart disease attributed to moderate drinking.