Extrahepatic lipogenesis contributes to hyperlipidemia in the analbuminemic rat

J. A. Joles, K. R. Feingold, A. Van Tol, L. H. Cohen, X. Sun, H. Jones, R. W. Davies, G. A. Kaysen, N. Willekes-Koolschijn, A. H. Moser, M. M. Geelhoed-Mieras, A. M. Griffioen

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13 Scopus citations

Abstract

Hepatic lipid and apolipoprotein synthesis is increased in the nephrotic syndrome. Catabolism of triglyceride-rich lipoproteins is impaired in nephrotic syndrome but not in rats with hereditary analbuminemia (NA), suggesting that lipid synthesis should be increased by analbuminemia in the absence of proteinuria. In this study the rate of cholesterol and fatty acid synthesis in liver and extrahepatic tissue was measured in female NA and control Sprague-Dawley (SD) rats to determine whether lipid synthesis was indeed increased in isolated analbuminemia and to identify the site(s) of increased lipogenesis. We also measured the concentrations of apolipoproteins (apo) AI, B, and E in plasma, as well as the levels of the respective mRNAs in liver. Plasma cholesterol, triglycérides, and apo AI, B, and E were all increased severalfold in the NA rat (P < 0.001). Although liver apolipoprotein mRNA content was significantly increased (P < 0.001) for apo AI (643%), B (273%), and E (299%), 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in liver microsomes and hepatic cholesterol synthesis were not significantly increased in the NA rats. Hepatic fatty acid synthesis and intestinal cholesterol synthesis were not increased in the NA rats. Surprisingly, intestinal fatty acid synthesis was elevated by 60% (P < 0.01). The NA rats demonstrated approximately fourfold increases in the incorporation of 3H2O into circulating cholesterol and fatty acids (P < 0.001). A 56% increase in the synthesis of total nonsaponifiable lipid was found in the extravisceral carcass (P < 0.01). Thus, although apolipoprotein mRNAs encoding the principal apolipoprotein are increased in the liver of the NA rat, suggesting that the liver is an important site of increased apolipoprotein synthesis, the liver is not the site of increased lipogenesis. Major increases in cholesterol and fatty acid synthesis occur at extrahepatic sites in analbuminemia.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume265
Issue number1 34-1
StatePublished - 1993

Keywords

  • 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity
  • Analbuminemia
  • Apolipoprotein
  • Cholesterol synthesis
  • Fatty acid synthesis

ASJC Scopus subject areas

  • Physiology

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    Joles, J. A., Feingold, K. R., Van Tol, A., Cohen, L. H., Sun, X., Jones, H., Davies, R. W., Kaysen, G. A., Willekes-Koolschijn, N., Moser, A. H., Geelhoed-Mieras, M. M., & Griffioen, A. M. (1993). Extrahepatic lipogenesis contributes to hyperlipidemia in the analbuminemic rat. American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 265(1 34-1).