The effects of cholesterol/fat feeding on lipid levels and morphological structures in liver, kidney and spleen in guinea pigs.

Guinea pigs were fed a semisynthetic diet containing 10 per cent (by weight) cottonseed oil with or without 1 per cent cholesterol. In the animals fed fat, the lipid levels and the morphology remained normal in all tissues studied. Concomitantly with a marked accumulation of cholesteryl ester (CE) in the liver, however, many microscopical changes occurred in guinea pigs fed cholesterol/fat. A prominent deposition of lipids in vacuoles, mostly without delimitating membranes, where observed at centrilobular sites. Multivacuolated, secondary lysosomes, membrane bound lipid vacuoles (lipolysosomes) and myelin figures were found both in hepatocytes and Kupffer cells. Myelin figures and crystalline clefts were observed more often in Kupffer cells than in hepatocytes. The granular endoplasmic reticulum in the Kupffer cells was grossly dilated and filled with an amorphous material. Both the biochemical and the morphological findings in hepatocytes and Kupffer cells are very similar to those observed in cholesteryl ester storage disease and in Wolman's disease. These two lipid storage diseases are both related to deficiency of an acid lipase in the liver. Measurement of the acid liver CE hydrolase in guinea pigs fed fat and in those fed cholesterol/fat showed similar activity. A relative deficiency of this enzyme activity could be the reason for the development of the enormous CE storage in guinea pig livers. These findings suggest that guinea pigs fed cholesterol/fat, in some respects, can be used as a model for Wolman's disease and cholesteryl ester storage disease. We did not find any microscopical changes in the kidneys from animals fed cholesterol/fat, thus indicating that the experimental condition it not useful as a model for studies of the kidney changes in lecithin:cholesterol acyltransferase (LCAT) deficiency.