Serum lipoprotein accumulation in the livers of orotic acid-fed rats

This study provides confirmation of previous observations that showed that rats fed a diet containing 1% orotic acid for 7 days develop a fatty liver and that there is an inhibition of the secretion of low density lipoproteins without altering general liver protein synthesis. Accumulated fat droplets (liposomes) are entrapped within rough endoplasmic reticulum vesicles. In this study, these vesicles have been shown to accumulate the apolipoproteins of low and very low density lipoproteins. Inhibition of lipoprotein secretion was demonstrated by perfusion of livers from orotic acid-fed rats with a serum-free medium. Liposomes were isolated from these rats. Partially delipidated liposomes, but not similarly treated microsomes or cell sap, were found to form a precipitation line when reacted against anti-low density lipoprotein antiserum. Detergent solubilization of the liposome followed by density gradient centrifugation resulted in a peak at d 1.025 g/ml containing both lipid and protein. Acrylamide electrophoresis in 8 m urea after total delipidation demonstrated liposomal bands which coelectrophoresed with three of four very low density lipoprotein bands; there was no band corresponding to the very low density lipoprotein band which travels furthest in acrylamide electrophoregrams. However, acrylamide electrophoresis of the apoproteins of serum high density lipoprotein from orotic acid-fed animals revealed the presence of the latter band. The results indicate that liver liposomes from orotic acid-fed rats apparently contain the low density apoprotein and probably several other very low density lipoprotein peptides.