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.