EFFECT OF LIPOPROTEIN-X ON LIPID-METABOLISM IN RAT-KIDNEY

Lipoprotein-X (Lp-X) is found in the plasma of patients with familial lecithin: cholesterol acyltransferase (LCAT) deficiency syndromes. The majority of the patients with this disorder develop progressive glome rulosclerosis. In this study, the effect of Lp-X on lipid metabolism i n perfused rat kidney was investigated. Lp-X was isolated from plasma of patients with familial LCAT deficiency by sequential ultracentrifug ation and gel filtration column chromatography. Rat kidneys were perfu sed for 1-2 h with Krebs-Henseleit buffer containing 20 mu M [1-C-14]a cetate or 20 mu M [Me-H-3]choline. In the presence of Lp-X, no signifi cant difference in the incorporation of radioactivity into triglycerid es, cholesterol, phosphocholine, CDP-choline and sphingomyelin was obs erved. However, incorporation of radioactivity into cholesteryl esters and phosphatidylcholine was significantly elevated in Lp-X perfused k idneys. The contents of cholesterol, cholesteryl esters and phosphatid ylcholine were also significantly increased in Lp-X perfused kidneys. The increase in lipid content in the Lp-X perfused kidney is attribute d to the direct deposition of Lp-X lipids into the organ. The increase in the labelling of cholesteryl esters was attributed to the increase of available substrate (choresterol) for the acyl-CoA:cholesterol acy ltransferase (ACAT) reaction. The increase in phosphatidylcholine labe lling was caused by a reduced turnover of the newly synthesized labell ed phosphatidylcholine during Lp-X perfusion.