Hyperlipoproteinemia in experimental chronic renal insufficiency in the rat

Hyperlipoproteinemia in experimental chronic renal insufficiency of the rat. Lipid metabolism was studied in experimental uremia. Uremic (U) rats were compared with sham-operated, pair-fed (PF) controls and with ad-lib-fed (AL) controls. In U animals, fasting glucose concentrations were normal, immunoreactive serum insulin (IRI) levels were decreased, and immunoreactive glucagon levels were increased. A significant increase in the serum concentration of all lipid classes was observed: triglycerides were elevated 10-fold above the values in PF and AL controls; phospholipids, twofold; total cholesterol, threefold; and free cholesterol, sixfold. Cholesterol concentration was increased in beta- and pre-beta-lipoproteins and even more so in alpha- and pre-alpha-lipoproteins. There was an increase in the ratio of free cholesterol/total cholesterol. The fatty acid composition of serum lipoproteins was unchanged. Concomitantly, in liver tissue, there was no change in lipid content (triglyceride, cholesterol) and fatty acid composition. These findings argue against glucose- or insulin-mediated changes in hepatic de novo fatty acid synthesis, chain elongation, or poly-desaturation. In U animals, the HMG-CoA-reductase activity of liver microsomes was slightly, but not significantly, reduced as was tritiated water incorporation into cholesterol in isolated perfused liver preparations. In adipose tissue, there was a decrease in triglyceride content. The results provide evidence against insulin-mediated hepatic overproduction as a major cause of hyperlipoproteinemia in this model of experimental renal insufficiency and point to peripheral under-utilization of lipoproteins. Hyperlipoprotéinémie de l'insuffisance rénale expérimentale chez le rat. Le métabolisme des lipides a été étudié dans l'urémie expérimentale. Des rats urémiques (U) ont été comparés à des témoins ayant subi un simulacre d'intervention et nourris de façon identique (PF) et à des témoins nourris ad lib (AL). Chez les animaux U la glycémie à jeun est normale, l'insuline immunoréactive sérique (IRI) est diminueé et le glucagon immunoréactif est augmenté. Une augmentation significative de toutes les classes de lipides sériques est observée. Les triglycérides sont supérieurs de 10 fois aux valeurs de PF et de AL, les phospholipides de deux fois, le cholestérol total de trois fois et le cholestérol libre de six fois. La concentration de cholestérol est augmentée dans les bêta et les pré-bêta lipoprotéines et