Defective lipolysis persists in hearts of rats with Heymann nephritis in the absence of nephrotic plasma

George Kaysen, X. M. Pan, W. G. Couser, I. Staprans

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Catabolism of triglyceride-rich lipoproteins, including chylomicrons (CM), is reduced in the nephrotic syndrome. It has been suggested that hyperlipidemia per se might lead to reduced CM catabolism by saturating catabolic sites. Evidence also implicates disordered high-density lipoprotein function as reducing the activity of lipoprotein lipase (LPL), the final effector of CM lipolysis. To establish whether CM lipolysis would be abnormal in the absence of either abnormal rat lipoproteins or hyperlipidemia, we measured CM lipolysis by isolated perfused hearts of rats with passive Heymann nephritis. We found that lipolysis was significantly reduced by 30% at 30 minutes (246 ± 40 μmol v 164 ± 10 μmol fatty acid released/hr, P < 0.05). Uptake of fatty acids was also significantly less in nephrotic hearts than in control hearts (7.25% ± 0.93% of dose v 3.32% ± 0.011% of dose, P < 0.01). Total heart LPL activity was reduced by 40% in hearts of nephrotic animals (368.5 ± 39.4 μmol v 210.6 ± 25.9 μmol free fatty acid released/hr/g heart, P < 0.01). The heparin-releasable LPL pool is that pool bound to the vascular endothelium and represents the biologically active fraction. We perfused hearts with heparin and found that heparin-releasable LPL was reduced by an order of magnitude in hearts from nephrotic rats (173 ± 33 μmol v 19.4 ± 11.7 μmol free fatty acid released/hr/heart, P < 0.001). The decrease in this pool represented nearly entirely the difference in total heart LPL in the two groups. Thus, Heymann nephritis causes reduced lipolysis of CM by isolated hearts in the absence of other rat lipoproteins and in the absence of increased lipid levels. Decreased lipolysis is associated with reduced activity of LPL on the cardiac endothelium, providing a potential mechanism for the reduced CM clearance in the nephrotic syndrome.

Original languageEnglish (US)
Pages (from-to)128-134
Number of pages7
JournalAmerican Journal of Kidney Diseases
Volume22
Issue number1
StatePublished - 1993

ASJC Scopus subject areas

  • Nephrology

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