Both peripheral chylomicron catabolism and hepatic uptake of remnants are defective in nephrosis.
We showed previously that proteinuria caused delayed chylomicron (CM) clearance in the rat and postulated the existence of a primary defect in CM hydrolysis. It was possible that reduced CM clearance resulted from increased lipogenesis causing saturation of catabolic sites and not from a primary defect in CM catabolism. To clarify this point we measured kinetically the absolute rate of triglyceride (TG) uptake from CM in rats with Heymann nephritis (HN) and normal Sprague-Dawley rats (SD) and determined TG uptake in individual tissues using [3H]TG- and [14C]cholesterol-labeled CM. Hepatic [14C]cholesterol uptake was reduced in HN (69.3 +/- 6 vs. 7.2 +/- 2% of dose, P less than 0.001). TG uptake was reduced in HN measured kinetically (1.01 +/- 0.09 vs. 0.213 +/- 0.028 mg TG.min-1.100 g body wt-1, P less than 0.001) and reduced in all tissues (heart, skeletal muscle, fat, and liver). CM are catabolized on the vascular endothelium to atherogenic, cholesterol-rich remnant (CM remnant) particles, which are then rapidly taken up by the liver. We measured hepatic CM remnant uptake in SD and in HN using [14C]cholesterol-labeled CM remnant. CM remnant uptake was significantly reduced in HN (58 +/- 1.2 vs. 20 +/- 0.86% uptake, P less than 0.01). CM remnants were increased significantly in plasma of HN. Thus the nephrotic syndrome causes a primary defect in the uptake of TG from CM that is expressed in all tissues and a separate defect in hepatic CM remnant uptake. Although CM remnant generation is impaired because of defective CM hydrolysis, the defect in hepatic CM remnant uptake is so severe that these particles accumulate in blood, posing a potential risk for atherogenesis.
Kaysen
G A
GA
Department of Medicine, University of California, Davis 95616.
Mehendru
L
L
Pan
X M
XM
Staprans
I
I
D000818:Animals; D002914:Chylomicrons / Q000378:metabolism*; D005921:Glomerulonephritis / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D002914:Chylomicrons; D010446:Peptide Fragments; D014280:Triglycerides