Susan L. Burditt

Effects of starvation, corticotropin injection and ethanol feeding on the activity and amount of phosphatidate phosphohydrolase in rat liver

Phosphatidate phosphollydr~lase has an important regulatory role in hepatic glycerolipid synthesis, especially in faciIitating an increased synthesis of triacylglycerols [ 1,2]. Many of the changes observed in this activity are brought about by glu~o~orti~oids [3-S j, but other mechanisms also seem to be involved [5-lo]. This paper describes the preparation of an antibody against the soluble phosphatidate phosphohydrolase of rat liver. It was used to investigate the extent to which some changes in this phosphohydrolase activity resulted from alterations in its concentration. To the best of our knowledge, this is the first report of this type of experiment with phospilatidate phosphohydrolase. This activity decreased after starving rats for 24 h, but the amount of the phosphohydrolase relative to DNA was unchanged. The amount of the phosphohydrolase increased by -3.5-fold at 400 min after injecting ~orticotrapin~ whereas the activity increased by 2..5-fold. At 400 min after feeding with. ethanol the phosphohydrolase activity and amount were increased by 7-and 6.3-fold, respectively. The increases in phosphohydrolas~ concentration were probably mediated by corticosterone. It also appears likely that the phosphohydrolase is capable of being activated and inactivated since changes in amount were not necessarily paralleled by changes in activity.

The mode of action of fenfluramine and its derivatives and their effects on glycerolipid metabolism

SummaryThe evidence is reviewed that fenfluramine and benfluorex could have both direct and indirect effects in decreasing the rate of triacylglycerol synthesis in the liver. The direct effect is mediated through the inhibition of phosphatidate phosphohydrolase and by the recycling of excess phosphatidate back to glycerol phosphate. The indirect effect involves alteration of the concentrations of glucocorticoids in the blood and this was demonstrated with rats treated chronically with benfluorex. In these animals, the extent of ethanol-induced increases in serum corticosterone, in hepatic phosphatidate phosphohydrolase activity, and in the synthesis and accumulation of triacylglycerol in the liver was diminished. It is also suggested that glucocorticoids are responsible for the increased synthesis of hepatic triacylglycerols that is seen in diabetes and in stress conditions, and after eating fructose, glycerol, sorbitol and saturated fat. A combination of these direct and indirect effects could contribute...

The effects of administering N‐(2‐benzoyloxyethyl) norfenfluramine to rats on the hepatic synthesis of glycerolipids

N‐(2‐Benzoyloxyethyl) norfenfluramine (S‐780) was administered to rats by stomach tube at a dose of 50 mg kg−1 of body weight. Livers of the rats which were given an acute dose of the drug synthesized more triacylglycerol, phosphatidylcholine and phosphatidylethanolamine from [1,3‐3H]glycerol and [14C]palmitate than did those of control rats. The measurements were made by injecting a mixture of the radioactive precursors into the portal veins of anaesthetized rats and freeze clamping a portion of the liver 1 min later. Different results were obtained after treating rats daily with S‐780 for 5 days. Liver slices from these rats synthesized less triacylglycerol and relatively more phosphatidylinositol plus phosphatidyl‐serine from [3H]glycerol than did those of control rats. S‐780 treatment depressed the hepatic synthesis of phosphatidylcholine and phosphatidylethanolamine as measured in vivo after intraportal injection of [14C]palmitate and [3H]glycerol. Chronic treatment with S‐780 also depressed food intake and lowered liver weight and body weight of rats fed the 41B diet. The results are discussed in relation to the effects of S‐780 on the synthesis of glycerolipids.

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.