Alcoholic Fatty Liver In Mice Research Articles

Role of Adiponectin in the Protective Action of Dietary Saturated Fat Against Alcoholic Fatty Liver in Mice * #

The protective effect of dietary saturated fatty acids against the development of alcoholic liver disease has long been known, but the underlying mechanism is not completely understood. We examined the involvement of the adipocyte hormone adiponectin. Circulating adiponectin levels were significantly elevated by chronic ethanol administration to mice consuming a diet high in saturated fat. The increase in circulating adiponectin was associated with the activation a set of hepatic signaling pathways mediated through AMP-activated protein kinase, PPAR-alpha, and PPAR-gamma coactivator alpha, which in turn led to markedly increased rates of fatty acid oxidation, prevention of hepatic steatosis, and alleviation of liver enzyme changes. Furthermore, treatment of rat 3T3-L1 adipocytes with saturated fatty acids (palmitic or stearic acids) in the presence of ethanol increased secretion of adiponectin and enhanced activity of a mouse adiponectin promoter. In conclusion, the protective action of saturated fat against the development of alcoholic fatty liver in mice is partially mediated through induction of adiponectin. The present findings suggest a novel paradigm for dietary fatty acids in the pathogenesis of alcoholic liver disease and provide a promising therapeutic strategy-nutritional modulation of adiponectin-in treating human alcoholic fatty liver disease.

Comparison of hepatic triglyceride content and hepatic lipid secretion after various doses of ethanol

The effect of ethanol (1, 2 and 4 mg/g i.v.) on hepatic triglyceride content, hepatic lipid release and plasma esterified fatty acid levels was investigated in mice. Within 4–8 hr all doses of ethanol increased the triglyceride content of the liver to about the same degree. Lipid secretion from the liver was inhibited 2 hr after the administration of 4 mg/g ethanol and increased 8 hr after the injection of 2 and 4 mg/g ethanol. Plasma esterified fatty acids showed an initial increase after 1 mg/g and an initial decrease after 4 mg/g ethanol. Eight hr after the administration of 4 mg/g ethanol the level of esterified fatty acids in the plasma was increased. Two mg/g ethanol did not have any effect on plasma esterified fatty acid levels. From the absence of a clear correlation of the three parameters tested it is concluded that inhibition of lipid secretion from the liver is not a major reason for the development of acute alcoholic fatty liver in mice.