Lipid metabolism in the blood and liver of rats was investigated to clarify the mechanism of dyslipoproteinemia in the nephrotic syndrome. The nephrotic syndrome was induced in rats by a single injection of daunomycin. The serum total cholesterol, triglyceride, and phospholipid levels in nephrotic rats 14 days after the injection were increased 3.1-fold, 2-fold, and 2.7-fold, respectively, over the control values. The cholesterol, triglyceride, and phospholipid contents of high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) were also increased, increase in VLDL lipids being the greatest. The serum HDL cholesterol level decreased gradually after day 14, returning to the normal level on day 37, whereas the LDL and VLDL cholesterol levels continued to increase until day 37. The mechanism of dyslipoproteinemia in the nephrotic syndrome was examined by comparing lipid metabolism in the liver of nephrotic rats induced by daunomycin with that of rats fed on high-cholesterol diet. The contents of total lipids, triglyceride, and cholesterol ester in the liver were significantly less in nephrotic rats than in controls. The contents of total lipids and cholesterol ester in the liver were much higher in rats fed on high-cholesterol diet than in controls. The contents of total lipids, triglyceride, cholesterol ester, and phospholipid in the liver were significantly lower in nephrotic rats fed on high-cholesterol diet than in normal rats fed on high-cholesterol diet. [1- 14C]Acetate incorporation into liver lipids was higher in nephrotic rats and lower in rats fed on high-cholesterol diet than in controls. [1- 14C]Palmitate incorporation into liver lipids was higher in nephrotic rats and rats fed on high-cholesterol diet than in controls. These data suggest that discharge of lipids, de novo synthesis of lipids, and utilization of preformed free fatty acids were all stimulated in the liver of rats with the nephrotic syndrome induced by daunomycin. However, although the utilization of preformed free fatty acids was stimulated, de novo synthesis of lipids was suppressed in the liver of rats fed on high-cholesterol diet.
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