An Orotic Acid-induced, Adenine-reversed Inhibition of Hepatic Lipoprotein Secretion in the Rat

The induction of a severe fatty liver in rats by the addition of erotic acid to their purified diets was first reported by Standerfer and Handler (1). Creasey, Hankin, and Handschumacher (2) found that the liver fat was largely triglyceride and observed that its accumulation was both prevented and reversed by supplementing the erotic acid diets further with adenine (3). Marked alterations in the concentration of various acid-soluble nucleotides of liver also result from the ingestion of erotic acid, with a 400 70 elevation of uridine nucleotides and a 50 70 depression in adenine nucleotides being the most prominent (4). The mechanism by which dietary erotic acid and adenine alter lipid metabolism is unknown and is the subject of this investigation. Several experimental approaches were used and the following parameters were studied: (a) the effect of altering dietary protein and fat levels on the action of erotic acid; (b) the fatty acid composition of accumulated liver lipids of rats fed a fat-free erotic acid diet; (c) the effect of erotic acid on lipogenesis and fat transport as measured by the incorporation in viva of tritium from labeled body water into the fatty acids of various body compartments; (d) the effect of dietary erotic acid and adenine on the lipid, glucose, and protein content of plasma; and (e) the effect of dietary erotic acid on the hyperlipemia induced by the intravenous injection of a nonionic surface-active agent. From these studies it is concluded that the fatty liver induced by erotic acid results from a severe inhibition of hepatic lipoprotein secretion, and that the addition of adenine to the diet rapidly reverses this inhibition.