Studies on the Pathogenesis of the Ethanol-induced Fatty Liver. II. Effect of Ethanol on Palmitate-1-C14 Metabolism by the Isolated Perfused Rat Liver*

Abstract

In man and in the experimental animal, a fatty liver can result from acute or chronic ethanol ingestion. In the rat an increase in liver lipid occurs either after a single intoxicating dose of ethanol or after the chronic administration of this drug (2, 3). The lipid that accumulates in the liver under these conditions is predominantly in the form of triglycerides (4).The production of a fatty liver would appear to involve one or more of five possible mechanislms: a) increased mobilization of fatty acids from the peripheral adipose depots to the liver, b) increased de novo synthesis! of fatty acids by the liver, c) decreased hepatic catabolism (e.g., oxidation) of fatty acids, d) increased or preferential esterification of fatty acids to triglycerides, or e) a decreased release of lipid from the liver. In considering these mechanisms, it should be noted that studies by Mallov (5) and by Brodie and Maickel (4) have demonstrated an increased mobilization of plasma free fatty acids after relatively large doses of ethanol; this effect is apparently mediated through hypophyseal-adrenal pathways and the sympathetic nervous system (4). Furthermore, the fatty liver produced by ethanol contains large amounts of linoleic acid that is stored in the adipose tissue but not synthesized by mammalian liver (6). Lieber and Schmid (7) have observed that ethanol stimulates

Role of dietary, adipose, and endogenously synthesized fatty acids in the pathogenesis of the alcoholic fatty liver.

“…Decreased release of lipoproteins from the liver has been proposed as a mechanism for the fatty liver produced on carbon tetrachloride intoxication (31), and on the the basis of data obtained in vitro with perfusion of livers and large amounts of alcohol it has also been suggested that this may play a role in the pathogenesis of the alcoholic fatty liver (32). It has been shown, however, that both in man (3,10,33,34) and in rats (35) large doses of alcohol produce an increase of circulating blood lipids, at least during the initial period of intoxication, lasting up to 2 weeks (33,34).…”

Golgi Fractions Prepared From Rat Liver Homogenates

“…62,63) . It is generally assumed that the rates of synthesis of fatty acids (64) and triglycerides rise (65) as a result of an increase in the NADH :NAD ratio in the cytoplasm (66), but a decrease in the rate of discharge (67) Distance from origin (cm) FIGURE 6 Chromatographic profile of the products of the UDP-galactose :N-acetylglucosamine galactosyltransferase . Assay carried out with 60 µg protein without Triton X-100 .…”

Hepatocyte growth factor leads to recovery from alcohol-induced fatty liver in rats

“…The immune complexes were separated by SDS-PAGE, visualized by autoradiography, and scanned using a densitometer. The amount of TCA-precipitable 35 S-labeled proteins was measured to determine total protein synthesis.…”