Abstract
The authors studied xanthomatous skin in cholesterol-fed rabbits for changes in lipid content and in activities of enzymes regulating intracellular lipid content. After 80 days of hypercholesterolemic diet, xanthomas were widespread and changes in lipid metabolism were marked. In both tissue homogenates and cell membrane pellets, unesterified cholesterol and phospholipids increased 2-fold to 6-fold, and cholesteryl esters increased about 30-fold. Tissue triglycerides, however, decreased to half the levels found in control skin. Cholesterol esterification rates, measured by activity of acyl coenzyme A: cholesterol acyltransferase, increased moderately to markedly; hydrolase activity against 4-methylumbelliferyl oleate also increased at both acid and neutral pH, but hydrolase activity against cholesterol oleate increased only at acid pH. Thus, hypercholesterolemia caused striking increases in intracellular cholesterol esterification rates, increases in lipase activity at both neutral and acid pH, and increases in cholesteryl ester hydrolase activity at acid pH. Increases in cholesterol-esterifying activity uniformly exceeded increases in cholesteryl ester hydrolytic activity in congruence with net accumulation of cholesteryl ester. Skin xanthoma grade, however, had no consistent relation to the cholesterol esterification rates. Instead, the enzyme data suggested that marked abnormalities of lipid metabolism are diffusely distributed through dermal tissue as a precondition for the focal emergence of xanthomas.
Full text
PDF









Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Armstrong M. L., Connor W. E., Warner E. D. Xanthomatosis in rhesus monkeys fed a hypercholesterolemic diet. Arch Pathol. 1967 Sep;84(3):227–237. [PubMed] [Google Scholar]
- Belfrage P., Vaughan M. Simple liquid-liquid partition system for isolation of labeled oleic acid from mixtures with glycerides. J Lipid Res. 1969 May;10(3):341–344. [PubMed] [Google Scholar]
- Berge R. K., Thomassen M. S. Effects of high fat diets on the activity of palmitoyl-CoA hydrolase in rat liver. Lipids. 1985 Jan;20(1):49–52. doi: 10.1007/BF02534363. [DOI] [PubMed] [Google Scholar]
- Brecher P., Chobanian J., Small D. M., Chobanian A. V. The use of phospholipid vesicles for in vitro studies on cholesteryl ester hydrolysis. J Lipid Res. 1976 May;17(3):239–247. [PubMed] [Google Scholar]
- Brown M. S., Goldstein J. L., Krieger M., Ho Y. K., Anderson R. G. Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins. J Cell Biol. 1979 Sep;82(3):597–613. doi: 10.1083/jcb.82.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bulkley B. H., Buja L. M., Ferrans V. J., Bulkley G. B., Roberts W. C. Tuberous xanthoma in homozygous type II hyperlipoproteinemia. A histologic, histochemical, and electron microscopical study. Arch Pathol. 1975 Jun;99(6):293–300. [PubMed] [Google Scholar]
- Cortner J. A., Coates P. M., Swoboda E., Schnatz J. D. Genetic variation of lysosomal acid lipase. Pediatr Res. 1976 Nov;10(11):927–932. doi: 10.1203/00006450-197611000-00005. [DOI] [PubMed] [Google Scholar]
- FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
- Gillies P. J., Bell F. P. Arterial and plasma carnitine levels in rabbits: influence of age and dietary cholesterol. Exp Mol Pathol. 1976 Dec;25(3):402–411. doi: 10.1016/0014-4800(76)90048-4. [DOI] [PubMed] [Google Scholar]
- Haley N. J., Fowler S., de Duve C. Lysosomal acid cholesteryl esterase activity in normal and lipid-laden aortic cells. J Lipid Res. 1980 Nov;21(8):961–969. [PubMed] [Google Scholar]
- Kelley J. L., Suenram C. A., Valente A. J., Sprague E. A., Rozek M. M., Schwartz C. J. Evolution of foam cells in subcutaneous rabbit carrageenan granulomas. II. Tissue and macrophage lipid composition. Am J Pathol. 1985 Sep;120(3):391–401. [PMC free article] [PubMed] [Google Scholar]
- Kodama H., Arakawa K., Nagao Y., Tada J., Masuda T., Nohara N. An experimental model of xanthoma by intradermal dextran sulfate injection. J Dermatol. 1979 Aug;6(4):239–245. doi: 10.1111/j.1346-8138.1979.tb01907.x. [DOI] [PubMed] [Google Scholar]
- Kodama H., Nagao Y., Arakawa K., Tada J., Nohara N. Cholesterol synthesis and esterification in experimental xanthoma tissues. J Lipid Res. 1981 Sep;22(7):1033–1041. [PubMed] [Google Scholar]
- Lees M. B., Paxman S. Modification of the Lowry procedure for the analysis of proteolipid protein. Anal Biochem. 1972 May;47(1):184–192. doi: 10.1016/0003-2697(72)90291-6. [DOI] [PubMed] [Google Scholar]
- Mathur S. N., Armstrong M. L., Alber C. A., Spector A. A. Hepatic acylcoenzyme A: cholesterol acyltransferase activity during diet-induced hypercholesterolemia in cynomolgus monkeys. J Lipid Res. 1981 May;22(4):659–667. [PubMed] [Google Scholar]
- Mathur S. N., Field F. J., Megan M. B., Armstrong M. L. A defect in mobilization of cholesteryl esters in rabbit macrophages. Biochim Biophys Acta. 1985 Mar 27;834(1):48–57. doi: 10.1016/0005-2760(85)90175-4. [DOI] [PubMed] [Google Scholar]
- Parker F., Short J. M. Xanthomatosis associated with hyperlipoproteinemia. J Invest Dermatol. 1970 Aug;55(2):71–88. doi: 10.1111/1523-1747.ep12291505. [DOI] [PubMed] [Google Scholar]
- Pitas R. E., Innerarity T. L., Mahley R. W. Foam cells in explants of atherosclerotic rabbit aortas have receptors for beta-very low density lipoproteins and modified low density lipoproteins. Arteriosclerosis. 1983 Jan-Feb;3(1):2–12. doi: 10.1161/01.atv.3.1.2. [DOI] [PubMed] [Google Scholar]
- Raheja R. K., Kaur C., Singh A., Bhatia I. S. New colorimetric method for the quantitative estimation of phospholipids without acid digestion. J Lipid Res. 1973 Nov;14(6):695–697. [PubMed] [Google Scholar]
- Sando G. N., Henke V. L. Recognition and receptor-mediated endocytosis of the lysosomal acid lipase secreted by cultured human fibroblasts. J Lipid Res. 1982 Jan;23(1):114–123. [PubMed] [Google Scholar]
- Spector A. A., Mathur S. N., Kaduce T. L. Role of acylcoenzyme A: cholesterol o-acyltransferase in cholesterol metabolism. Prog Lipid Res. 1979;18(1):31–53. doi: 10.1016/0163-7827(79)90003-1. [DOI] [PubMed] [Google Scholar]
- VAN HANDEL E., ZILVERSMIT D. B. Micromethod for the direct determination of serum triglycerides. J Lab Clin Med. 1957 Jul;50(1):152–157. [PubMed] [Google Scholar]
- WANG C. I., STRAUSS L., ADLERSBERG D. Experimental xanthomatosis in the rabbit. AMA Arch Pathol. 1957 Apr;63(4):416–422. [PubMed] [Google Scholar]
- von Hodenberg E., Khoo J. C., Jensen D., Witztum J. L., Steinberg D. Mobilization of stored triglycerides from macrophages as free fatty acids. Arteriosclerosis. 1984 Nov-Dec;4(6):630–635. doi: 10.1161/01.atv.4.6.630. [DOI] [PubMed] [Google Scholar]


