Catabolism of very low density lipoproteins in experimental nephrosis.

Abstract

Ab btract. The effects of experimental nephrosis in rats, produced by puromycin aminonucleoside, include an elevation of plasma levels of all lipoprotein density classes and the appearance of high density lipoprotein (HDL) rich in apoprotein (apo) A-I and deficient in apo A-IV and apo E. The hyperlipoproteinemia is associated with an increase in hepatic synthesis of lipoproteins. The possible role of decreased very low density lipoprotein (VLDL were obtained from nonfasting animals by ultracentrifugation at d 1.006 and included chylomicrons) catabolism and its relationship to the apolipoprotein composition of nephrotic high density lipoproteins (1.063 < d < 1.210, or 1.072 < d < 1.210 [HDL]) was explored.When 125I-VLDL was injected, the faster plasma clearance of lower molecular weight apolipoprotein B (apo BL) compared with that of higher molecular weight apo BH which is seen in normal rats was not observed in nephrotic rats. Less labeled phospholipid, apo C, and apo E were transferred from VLDL to higher lipoprotein density classes. Heparin-releasable plasma lipoprotein lipase and hepatic lipase activities were decreased by 50% in nephrotic rats compared with pair-fed controls. Perfusion of livers with medium that contained heparin released 50% less lipase activity in nephrotic rats than in controls.When heparin was injected intravenously, significant decreases in plasma levels of triglycerides and significant increases in levels of free fatty acids were observed in both groups of animals. In the nephrotic rats, 86% of the free fatty acids were in the lipoprotein fractions, as compared with 16% in the controls. Heparin treatment A portion of this work has been presented in abstract form

HDL abnormalities in nephrotic syndrome and chronic kidney disease

“…Under normal conditions, HDL binding to the SRB1 docking receptor in the liver accommodates hydrolysis and removal of its triglyceride and phospholipid contents by hepatic lipase 9 . In vitro analyses have demonstrated a marked reduction in heparin-releasable lipase activity in the livers of nephrotic rats compared to control rats 45 . Moreover, marked downregulation of hepatic lipase expression and activity in hypercholesterolaemic Imai rats with spontaneous focal segmental glomerulo sclero sis, and rats with puromycin aminoglycoside-induced nephrotic syndrome has also been reported 46,47 .…”

Effect of 3-thiadicarboxylic acid on lipid metabolism in experimental nephrosis.

“…46 Although possible effects of 3-thiadicarboxylic acid treatment on VLDL clearance were not specifically addressed in the present study, several observations indicated that the hypolipidemic properties of 3-thiadicarboxylic acid are probably not mediated by any major effect on VLDL catabolism. First, no effect on LDL receptor activity was seen, as discussed above.…”

Evidence for Catabolic Defect of Triglyceride in Experimental Nephrosis

“…These results raise a question about the previous concept that hyperlipidemia in nephrosis was mainly due to overproduction of lipoproteins in the liver2). It is unlikely that puromycin aminonucleoside may directly impair the liver function, so that the present results merely reflect the hepatic damages by the agent, because we used 10-14 days post-puromycin injected rats as an animals model of nephrosis, which is the similar experimental design reported by otherss, 9,11,16,19). In addition, Joven et al 28) recently reported that there was no consistant abnormal lesion in the liver of puromicin-induced nephrotic rats when observed either light or transmission electron microscopy.…”