The Role of Exogenous Lipids in the Hyperlipemia and Hypercholesteremia of Nephrotic Rats 1

Abstract

The renal disease, ascites, subcutaneous edema, and hyperlipemia induced in rats by injection of rabbit anti-rat kidney serum comprise a syndrome which closely resembles the nephrotic state as it occurs in humans (1). This provides a unique opportunity to study the mechanism(s) of the disturbed lipid metabolism of the nephrotic state. In previous studies from this laboratory it was found that the hypercholesteremia of nephrotic rats cannot be ascribed either to an increased intestinal absorption of dietary cholesterol (2) or to an increased hepatic synthesis of endogenous cholesterol (3). In the present study the role of exogenous lipids is further assessed, the data showing that the development of experimental nephrotic hyperlipemia and hypercholesteremia is independent of dietary fat. METHODS AND MATERIALTwenty male rats (Long-Evans strain), were injected intravenously with 0.5 ml. of rabbit anti-rat kidney serum (1) on each of two successive days. Seven of the rats (Group I) were fed a fat and sterol-free ration for five days prior to injection of immune serum, and continued to ingest this ration. Eight rats were fed stock laboratory ration (Group II) and five others (Group III) ingested stock ration supplemented with cholesterol (2 per cent of the diet) and cholic acid (1 per cent of the diet). The cholesterol and cholic acid-supplemented diet also was fed to six normal rats (Group IV) which were not injected with anti-kidney serum. A fifth group of ten other control rats (Group V) were fed stock ration.Each rat was bled from the tail six days after the injection of immune serum, and assay made according to previously described methods of the plasma concentrations of total cholesterol (4) and total lipids (5). Four days later similar determinations again were made in the rats ingesting stock ration (I) and the fat-sterol-free diet (II).X Aided by grants from the American Heart Association and research grant A-46 from the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Public Health Service. RESULTSSix days after the administration of immune serum all of the injected rats exhibited ascites, and lipemic-turbidity of their plasma. Table I presents the averages and ranges of plasma total lipids and total cholesterol values obtained from the nephrotic rats fed stock ration (Group II), those fed the diet free of fats and sterols (Group I), and the normal rats fed stock ration (Group V). The data show that the rats fed the fat-sterol-free diet developed a degree of hyperlipemia and hypercholesteremia equal to, or slightly greater than that developed by the nephrotic animals ingesting stock ration. The nephrotic rats of both groups exhibited a similar degree of ascites, subcutaneous edema, and grossly apparent turbidity of the plasma samples.The ingestion of a ration containing excess cholesterol and cholic acid has been shown to induce chronic hypercholesteremia in rats (6, 7), due to the increased intestinal absorption of cholesterol effected by simultaneous administration of...

The Causal Role of Plasma Albumin Deficiency in Experimental Nephrotic Hyperlipemia and Hypercholesteremia 1

“…This suggests of 528 course that, with the discontinuance of the albumin infusion, the experimental rats lost their artificially maintained elevated plasma albumin levels and in so doing, again became markedly hypercholesteremic and hyperlipemic. DISCUSSION Previously it was found that the hyperlipemia and hypercholesteremia of the nephrotic rat are of endogenous origin (2) and cannot be ascribed to any increased intestinal absorption (3) or decreased intestinal excretion (5). Moreover it was shown that the hepatic synthesis of cholesterol, the major source of the plasma cholesterol (19) is not increased in the nephrotic rat (4).…”

“…Previous studies (1)(2)(3)(4)(5)(6)(7)(8) from this laboratory have indicated that the hypercholesteremia and hyperlipemia occurring in the experimental nephrotic syndrome induced in rats by injection of anti-rat kidney seruim are due primarily to some intravascular "trapping" phenomenion whereby the animal appears unable to remove either endogenously-produced or dietary-derived cholesterol and lipid from the plasma with its customary efficiency. However, since renal changes seemingly initiate the total nephrotic syndrome, it seems probable that this "trapping" of cholesterol and lipid which occurs in the plasma in this syndrome is related in some manner to such renal changes.…”

Plasma Lipid Interrelationships in Experimental Nephrosis1

“…The results of previous studies from this laboratory have indicated that the increase of lipids in the nephrotic rat is an isolated accumulation of excess lipids which is confined, at least in the early phase, to its plasma (4) and which, although capable of intensification by ingestion of dietary lipid (5), stems primarily from endogenous sources (5). Our studies also indicated that the accumulation of cholesterol in the plasma in this syndrome is not caused by any preceding change in its intestinal absorption (2) or excretion (3), or in the rate of its hepatic synthesis (6).…”

The Distribution of Cholesterol and Total Lipids in the Nephrotic Rat 1

“…Previously, in various studies concerning cholesterol and lipid metabolism in the experimental nephrotic syndrome in rats, it was found that the characteristic hypercholesteremia observed in this disorder was of endogenous origin (3) and that it did not arise from an increased rate of cholesterol synthesis or discharge into the plasma by the liver (4) nor did it arise from any intrinsic failure within the liver to convert cholesterol into cholate (4). Subsequent studies also revealed that the hypercholesteremia was not due to either an increase in the rate of intestinal absorption (5) of cholesterol nor to a decrease in the rate of intestinal excretion of cholesterol (6).…”

“…This observed essential normality in the experimental nephrotic state of those processes concerned with the intestinal absorption and excretion of cholesterol as well as those concerned with the hepatic synthesis and conversion of cholesterol to cholate, of course, suggests that the hypercholesteremia occurring in this disorder is due to some failure in the transfer of cholesterol from the blood itself to the liver (3,7,8). If this last mechanism is responsible, then the nephrotic animal should exhibit an excess of cholesterol only in his blood and not in any other tissue or organ.…”