Both peripheral chylomicron catabolism and hepatic uptake of remnants are defective in nephrosis

George Kaysen, Leena Mehendru, X. M. Pan, Ilona Staprans

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Abstract

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 < 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 < 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 < 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume263
Issue number2 32-2
StatePublished - Aug 1992

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Keywords

  • Heymann nephritis
  • Hyperlipidemia
  • Nephrotic syndrome
  • Proteinuria
  • Triglycerides

ASJC Scopus subject areas

  • Physiology

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