Effects of chronic modification of dietary fat and carbohydrate on the insulin, corticosterone and metabolic responses of rats fed acutely with glucose, fructose or ethanol.

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

The involvement of glucocorticoids in regulating the activity of phosphatidate phosphohydrolase and the synthesis of triacylglycerols in the liver. Effects of feeding rats with glucose, sorbitol, fructose, glycerol and ethanol.

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.

The effect of dietary carbohydrate and fat on the activities of some enzymes responsible for glycerolipid synthesis in rat liver.

1. Male rats were fed for 14 days on diets containing (by wt.) 53% of starch, or on diets in which 20% of the starch was replaced by sucrose, corn oil or lard. 2. The hepatic activities of the microsomal glycerol phosphate acyltransferase, dihydroxyacetone phosphate acyltransferase, phosphatidate cytidylyltransferase, diacylglycerol acyltransferase and choline phosphotransferase, and of the soluble phosphatidate phosphohydrolase, were measured. 3. The soluble phosphatidate phosphohydrolase activity was higher in those rats fed on lard than in those fed on the starch diet. Choline phosphotransferase activity was higher in the rats fed on corn oil than in those fed on the starch diet. 4. The rate of hepatic glycerolipid synthesis was measured in vivo 1 min after injection of [1,3-3H]glycerol and [1-14C]palmitate into the portal veins. 5. The relative rate of phosphatidylcholine synthesis in vivo was increased after feeding with corn oil and the higher specific activity of choline phosphotransferase may contribute to this result. The equivalent rate of triacylglycerol synthesis was increased by feeding with lard rather than corn oil, and the increased activity of phosphatidate phosphohydrolase may partly explain this. The latter changes probably contribute to the increased concentration of triacylglycerol which other authors have observed in the livers and sera of animals fed on saturated and monounsaturated fats.

The effects of amphiphilic compounds on phosphatidate metabolism.

Amphiphilic cations interact with phosphatidate and thereby change its physical properties. This interaction can redirect phospholipid metabolism. In the presence of Mg2+ amphiphilic cations inhibit the activity of phosphatidate phosphohydrolase and stimulate that of phosphatidate cytidylyltransferase. Increasing the concentration of Mg2+ further, or adding Ca2+ have similar effects, except that Ca2+ does not stimulate phosphatidate cytidylyltransferase activity. Amphiphilic anions reverse the effects caused by the amphiphilic cations. The implication of these results are discussed in relation to the pharmacological effects of amphiphilic cationic drugs.

The effects of acute ethanol feeding and of chronic benfluorex administration on the activities of some enzymes of glycerolipid synthesis in rat liver and adipose tissue.

Rats were treated for 5 days with benfluorex [1-(3-trifluoromethylphenyl)-2-[N-(2-benzoyloxyethyl)amino]propane] or with suspending medium (controls). They were then intubated with an acute intoxicating dose of ethanol or with glucose of equivalent energy content. Treatment of the control rats with ethanol specifically increases the hepatic activity of the soluble phosphatidate phosphohydrolase by about 5-fold in 6 h. The equivalent increase for the benfluorex-treated rats were about 2-fold. The results are discussed in relation to the effects of ethanol and benfluorex on glycerolipid synthesis.

The effects of amphiphilic cationic drugs and inorganic cations on the activity of phosphatidate phosphohydrolase.

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.