Feeding rats with sorbitol, fructose, glycerol and ethanol increases the concentration of serum corticosterone without significantly altering the concentration of insulin. This increase appears to be partly responsible for the increases in the hepatic activity of phosphatidate phosphohydrolase (compared with rats fed glucose or 0.9% NaCl) that has been reported [Sturton, Pritchard, Han & Brindley (1978) Biochem. J. 174, 667--670] and the enhanced capacity of the liver to synthesize triacylglycerols. The ethanol-induced increase in phosphohydrolase activity was largely, but not completely, prevented by adrenalectomy.

1. Phosphatidate phosphohydrolase from the particle-free supernatant of rat liver was assayed by using emulsions of phosphatidate as substrate. 2. The inhibition of the phosphohydrolase by chlorpromazine was of a competitive type with respect to phosphatidate. The potency of various amphiphilic cationic drugs as inhibitors of this reaction was related to their partition coefficients into a phosphatidate emulsion. 3. The effect of chlorpromazine on the phosphohydrolase activity was complementary rather than antagonistic towards Mg2+. Chlorpromazine stimulated the phosphohydrolase activity in the absence of added Mg2+ and was able to replace the requirement for Mg2+. However, at optimum concentrations of Mg2+, chlorpromazine inhibited the reaction, as did Ca2+. The phosphohydrolase activity was also stimulated by Co2+ and to a lesser extent by Mn2+, Fe2+, Fe3+, Ca2+, spermine and spermidine when Mg2+ was not added to the assays. 4. It is concluded that the inhibition of phosphatidate phosphohydrolase by amphiphilic cations can largely be explained by the interaction of these compounds with phosphatidate, which changes the physical properties of the lipid, making it less available for conversion into diacylglycerol. 5. The implications of these results to the effects of amphiphilic cations in redirecting glycerolipid synthesis at the level of phosphatidate are discussed.

1. Male rats were fed for 14 days on powdered diets containing (by weight) 53% of starch, or on diets in which 20g of starch per 100g of diet was replaced by lard or corn oil. They were then fed acutely by stomach tube with a single dose of glucose, fructose or ethanol of equivalent energy contents, or with 0.15m-NaCl. The serum concentrations of corticosterone, insulin, glucose, glycerol, triacylglycerol and cholesterol were measured up to 6h after this treatment. 2. Feeding saline (0.9% NaCl) acutely to the rats maintained on the three powdered diets produced a small transient increase in circulating corticosterone that was similar to that in rats maintained on the normal 41B pelleted diet. 3. Feeding glucose acutely to the rats on the powdered diets produced peak concentrations of corticosterone that were 2-3-fold higher than those seen in rats maintained on the 41B diet. The duration of this response increased in the order starch diet

Male rats were kept for 14 days with alternating 12h periods of light and darkness. The hepatic activity of soluble phosphatidate phosphohydrolase and the concentration of serum insulin were maximum at about 2h after dark. The peak concentration of serum corticosterone occurred 2h before the dark period. It is proposed that corticosterone is partly responsible for the increased phosphohydrolase activity, and that this enables the liver to increase its capacity to synthesize triacylglycerols during the period of maximum feeding.