Experimental nephrotic syndrome: removal and tissue distribution of chylomicrons and very-low-density lipoproteins of normal and nephrotic origin.
Lymph chylomicrons and plasma VLDL, 14C-labelled in vivo, were isolated from normal and nephrotic rats and injected into normal or nephrotic recipients. In normal recipients, the half-life of chylomicrons of nephrotic vs. normal origin was significantly longer (5.2 +/- 0.5 vs. 3.5 +/- 0.4 min-1). The nephrotic chylomicrons were larger in size, deficient in apo-E and apo A-I, rich in triacylglycerol and cholesterol, but poor in phospholipids, indicating that factors related to composition affected their removal. The half-life of nephrotic vs. normal VLDL, given to normal recipients, was unexpectedly shorter, (4.5 +/- 0.2 vs. 5.8 +/- 0.2 min-1). The nephrotic VLDL were also triacylglycerol- and cholesterol-rich and phospholipid-poor, but had a large diameter spread and contained a dense fraction according to the zonal ultracentrifugation pattern, suggesting the presence of faster removable IDL-like particles. When nephrotic rats received normal particles, a pronounced removal delay was seen, paralleling the extent of plasma triacylglycerol elevation. The half-life of chylomicrons was 8.3 +/- 1.4 and 15.2 +/- 2.5 min-1 in moderately and severely nephrotic rats, respectively, that of VLDL was 11.72 +/- 2.1 and 37.8 +/- 7.1 min-1 correspondingly. The chylomicron-triacylglycerol uptake was reduced both by adipose tissues and muscles of normal or nephrotic recipients, with some increase in entry into lungs, kidneys and spleen. Tissue distribution patterns of VLDL-triacylglycerol was similar to that of chylomicrons, except that the liver took up approx. 90% of the label. The low share of triacylglycerol uptake by tissues rich in lipoprotein lipase indicates that the activity of this enzyme was unlikely to limit the rate of removal. Lipoprotein lipase activity in adipose tissue and heart was slightly decreased in moderately nephrotic rats and declined only by approx. 35% in severely nephrotic ones. These results indicate that the removal defect in nephrosis seems to be due, in part, to changes in the composition of triacylglycerol-rich particles, compromising their accessibility to lipolysis and, in part, to their abundance, saturating the lipolytic capacity.
Levy
E
E
Department of Biochemistry, Hadassah University Hospital, Jerusalem, Israel.
Ziv
E
E
Bar-On
H
H
Shafrir
E
E
D000818:Animals; D002914:Chylomicrons / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D009404:Nephrotic Syndrome / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution; D014280:Triglycerides / Q000378:metabolism
D002914:Chylomicrons; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D008071:Lipoprotein Lipase