IDENTIFICATION OF LIPOPROTEIN-X-LIKE PARTICLES IN RAT PLASMA FOLLOWING INTRALIPID INFUSION

Fasting rats were infused with 10% Intralipid for 24 hr (0.33 mL/h per 100 g body weight) and the plasma lipoproteins isolated and compared with those of fed animals and animals with bile duct ligatures as controls. There was a 6- to 10-fold increase in the free cholesterol and phospholipid content of total plasma in animals infused with Intralipid or with ligated bile ducts. The changes were largely restricted to the low density lipoproteins (d=1.019-1.063 g/mL) where free cholesterol and phospholipid increased 30- to 60-fold compared with fed control animals. Hydroxylapatite chromatography of the low density lipoprotein fractions of both Intralipid-infused and bile duct ligated animals yielded a subfraction which was rich in free cholesterol (27%), phosphatidylcholine (66%), and protein (6%); the latter was composed primarily of albumin and apo C proteins. The electrophoretic mobility and polyanionic precipitation properties of the abnormal lipoprotein were indistinguishable from those of lipoprotein X isolated from the animals with bile duct ligatures. The albumin in the abnormal lipoprotein from both groups of experimental animals was detected immunochemically only after delipidation of the lipoprotein. Twice as much of the lipoprotein X accumulated in Intralipid-infused than in the bile duct ligated animals. On rechromatography of the residual low density lipoprotein other subfractions could be isolated which possessed lipid and protein proportions intermediate between those of the lipoprotein X and of normal rat plasma low density lipoprotein. The activity of lecithin cholesterol acyl transferase was increased twofold in the Intralipid-infused animals when comapred with control animals, but it decreased by 50% in the animals with bile duct ligatures. It is concluded that the unusual lipoprotein X accumulates in the plasma of Intralipid-infused animals owing to incomplete clearance of the exogenous phospholipid, which mobilizes tissue cholesterol and in the form of vesicular particles serves as a lipid phase for apo C proteins. A comparable mechanism is suggested for the formation of lipoprotein X in the animals with bile duct ligature.