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.