Hepatic triacylglycerol synthesizing activity during progression of alcoholic liver injury in the baboon.
To study the effects of alcoholic liver injury on the ability of ethanol to promote hepatic fat accumulation and hyperlipemia, baboons were pair-fed liquid diets containing 50% of energy either as ethanol or as additional carbohydrate (controls) for 1 to 7 years. Alcohol consumption produced triacylglycerol accumulation in the liver, hypertriacylglyceridemia, and various degrees of liver injury, including cirrhosis. At the early stages of fatty liver (with or without perivenular fibrosis), there was increased activity of microsomal diacylglycerol acyltransferase and of both microsomal and cytosolic phosphatidate phosphohydrolase, with no changes in glycerol-3-phosphate acyltransferase. With progression of the liver injury and development of septal fibrosis and/or cirrhosis, the rate of hepatic triacylglycerol accumulation and the magnitude of the hyperlipemia decreased, despite continuous ethanol intake. These changes were associated with disappearance of the increases in microsomal diacylglycerol acyltransferase and cytosolic phosphatidate phosphohydrolase activities, whereas those of microsomal phosphatidate phosphohydrolase remained elevated and glycerol-3-phosphate acyltransferase was unaffected. Thus, changes in the activity of two enzymes of the triacylglycerol-synthesizing pathway, namely the microsomal diacylglycerol acyltransferase and the cytosolic phosphatidate phosphohydrolase, may contribute to the differences in the rate of hepatic triacylglycerol accumulation and the degree of hyperlipemia during progression of the alcoholic liver damage.
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D051048:Diacylglycerol O-Acyltransferase; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism*; D010215:Papio; D010711:Phosphatidate Phosphatase / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis*
D014280:Triglycerides; D000431:Ethanol; D000217:Acyltransferases; D005992:Glycerol-3-Phosphate O-Acyltransferase; D051048:Diacylglycerol O-Acyltransferase; D010711:Phosphatidate Phosphatase