Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1983 Jul;72(1):45–51. doi: 10.1172/JCI110983

Cholesterol feeding increases low density lipoprotein synthesis.

C J Packard, L McKinney, K Carr, J Shepherd
PMCID: PMC1129159  PMID: 6308052

Abstract

This study examines the effects of increased dietary cholesterol (6 eggs/d) on the metabolism of low density lipoproteins in a group of seven healthy volunteers. Egg supplementation raised high density and low density lipoprotein cholesterol levels by 18 and 40%, respectively. The composition of the low density lipoprotein was unaltered and therefore the number of circulating particles must have increased. Kinetic studies indicated that this was due primarily to a 23% rise in the rate of synthesis of the lipoprotein. Catabolism was also affected. The fractional removal rate of native low density lipoprotein fell by 10% (P less than 0.05). However, the clearance of the 1,2 cyclohexanedione-treated lipoprotein remained unchanged (control fractional clearance rate [FCR] = 0.188 pools/d; cholesterol feeding FCR = 0.183 pools/d). Therefore, the reduction in low density lipoprotein catabolism appeared to be due to a fall in receptor activity. Consequently, an increased sterol load (34.2 mumol/kg per d vs. 27.7 mumol/kg per d in the control phase, P less than 0.02) was channelled into the receptor-independent route during egg feeding.

Full text

PDF
45

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Applebaum-Bowden D., Hazzard W. R., Cain J., Cheung M. C., Kushwaha R. S., Albers J. J. Short-term egg yolk feeding in humans. Increase in apolipoprotein B and low density lipoprotein cholesterol. Atherosclerosis. 1979 Aug;33(4):385–396. doi: 10.1016/0021-9150(79)90031-5. [DOI] [PubMed] [Google Scholar]
  2. Connor W. E., Lin D. S. The intestinal absorption of dietary cholesterol by hypercholesterolemic (type II) and normocholesterolemic humans. J Clin Invest. 1974 Apr;53(4):1062–1070. doi: 10.1172/JCI107643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dietschy J. M., Wilson J. D. Regulation of cholesterol metabolism. I. N Engl J Med. 1970 May 14;282(20):1128–1138. doi: 10.1056/NEJM197005142822005. [DOI] [PubMed] [Google Scholar]
  4. Flaim E., Ferreri L. F., Thye F. W., Hill J. E., Ritchey S. J. Plasma lipid and lipoprotein cholesterol concentrations in adult males consuming normal and high cholesterol diets under controlled conditions. Am J Clin Nutr. 1981 Jun;34(6):1103–1108. doi: 10.1093/ajcn/34.6.1103. [DOI] [PubMed] [Google Scholar]
  5. Goldstein J. L., Brown M. S. Atherosclerosis: the low-density lipoprotein receptor hypothesis. Metabolism. 1977 Nov;26(11):1257–1275. doi: 10.1016/0026-0495(77)90119-6. [DOI] [PubMed] [Google Scholar]
  6. Goldstein J. L., Brown M. S. Familial hypercholesterolemia: pathogenesis of a receptor disease. Johns Hopkins Med J. 1978 Jul;143(1):8–16. [PubMed] [Google Scholar]
  7. Goldstein J. L., Brown M. S. The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem. 1977;46:897–930. doi: 10.1146/annurev.bi.46.070177.004341. [DOI] [PubMed] [Google Scholar]
  8. Kovanen P. T., Bilheimer D. W., Goldstein J. L., Jaramillo J. J., Brown M. S. Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1194–1198. doi: 10.1073/pnas.78.2.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Langer T., Strober W., Levy R. I. The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia. J Clin Invest. 1972 Jun;51(6):1528–1536. doi: 10.1172/JCI106949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. MATTHEWS C. M. The theory of tracer experiments with 131I-labelled plasma proteins. Phys Med Biol. 1957 Jul;2(1):36–53. doi: 10.1088/0031-9155/2/1/305. [DOI] [PubMed] [Google Scholar]
  11. Mahley R. W., Hui D. Y., Innerarity T. L., Weisgraber K. H. Two independent lipoprotein receptors on hepatic membranes of dog, swine, and man. Apo-B,E and apo-E receptors. J Clin Invest. 1981 Nov;68(5):1197–1206. doi: 10.1172/JCI110365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mahley R. W., Innerarity T. L., Pitas R. E., Weisgraber K. H., Brown J. H., Gross E. Inhibition of lipoprotein binding to cell surface receptors of fibroblasts following selective modification of arginyl residues in arginine-rich and B apoproteins. J Biol Chem. 1977 Oct 25;252(20):7279–7287. [PubMed] [Google Scholar]
  13. McGill H. C., Jr The relationship of dietary cholesterol to serum cholesterol concentration and to atherosclerosis in man. Am J Clin Nutr. 1979 Dec;32(12 Suppl):2664–2702. doi: 10.1093/ajcn/32.12.2664. [DOI] [PubMed] [Google Scholar]
  14. Mistry P., Miller N. E., Laker M., Hazzard W. R., Lewis B. Individual variation in the effects of dietary cholesterol on plasma lipoproteins and cellular cholesterol homeostasis in man. Studies of low density lipoprotein receptor activity and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in blood mononuclear cells. J Clin Invest. 1981 Feb;67(2):493–502. doi: 10.1172/JCI110058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nestel P. J., Poyser A. Changes in cholesterol synthesis and excretion when cholesterol intake is increased. Metabolism. 1976 Dec;25(12):1591–1599. doi: 10.1016/0026-0495(76)90112-8. [DOI] [PubMed] [Google Scholar]
  16. Nestel P., Tada N., Billington T., Huff M., Fidge N. Changes in very low density lipoproteins with cholesterol loading in man. Metabolism. 1982 Apr;31(4):398–405. doi: 10.1016/0026-0495(82)90117-2. [DOI] [PubMed] [Google Scholar]
  17. Nestel P., Tada N., Billington T., Huff M., Fidge N. Changes in very low density lipoproteins with cholesterol loading in man. Metabolism. 1982 Apr;31(4):398–405. doi: 10.1016/0026-0495(82)90117-2. [DOI] [PubMed] [Google Scholar]
  18. Packard C. J., Third J. L., Shepherd J., Lorimer A. R., Morgan H. G., Lawrie T. D. Low density lipoprotein metabolism in a family of familial hypercholesterolemic patients. Metabolism. 1976 Sep;25(9):995–1006. doi: 10.1016/0026-0495(76)90129-3. [DOI] [PubMed] [Google Scholar]
  19. Quintão E., Grundy S. M., Ahrens E. H., Jr Effects of dietary cholesterol on the regulation of total body cholesterol in man. J Lipid Res. 1971 Mar;12(2):233–247. [PubMed] [Google Scholar]
  20. Schonfeld G., Patsch W., Rudel L. L., Nelson C., Epstein M., Olson R. E. Effects of dietary cholesterol and fatty acids on plasma lipoproteins. J Clin Invest. 1982 May;69(5):1072–1080. doi: 10.1172/JCI110542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shekelle R. B., Shryock A. M., Paul O., Lepper M., Stamler J., Liu S., Raynor W. J., Jr Diet, serum cholesterol, and death from coronary heart disease. The Western Electric study. N Engl J Med. 1981 Jan 8;304(2):65–70. doi: 10.1056/NEJM198101083040201. [DOI] [PubMed] [Google Scholar]
  22. Shepherd J., Bedford D. K., Morgan H. G. Radioiodination of human low density lipoprotein: a comparison of four methods. Clin Chim Acta. 1976 Jan 2;66(1):97–109. doi: 10.1016/0009-8981(76)90376-4. [DOI] [PubMed] [Google Scholar]
  23. Shepherd J., Bicker S., Lorimer A. R., Packard C. J. Receptor-mediated low density lipoprotein catabolism in man. J Lipid Res. 1979 Nov;20(8):999–1006. [PubMed] [Google Scholar]
  24. Shepherd J., Packard C. J., Bicker S., Lawrie T. D., Morgan H. G. Cholestyramine promotes receptor-mediated low-density-lipoprotein catabolism. N Engl J Med. 1980 May 29;302(22):1219–1222. doi: 10.1056/NEJM198005293022202. [DOI] [PubMed] [Google Scholar]
  25. Shepherd J., Packard C. J., Grundy S. M., Yeshurun D., Gotto A. M., Jr, Taunton O. D. Effects of saturated and polyunsaturated fat diets on the chemical composition and metabolism of low density lipoproteins in man. J Lipid Res. 1980 Jan;21(1):91–99. [PubMed] [Google Scholar]
  26. Slater H. R., Packard C. J., Bicker S., Shepherd J. Effects of cholestyramine on receptor-mediated plasma clearance and tissue uptake of human low density lipoproteins in the rabbit. J Biol Chem. 1980 Nov 10;255(21):10210–10213. [PubMed] [Google Scholar]
  27. Slater H. R., Packard C. J., Shepherd J. Measurement of receptor-independent lipoprotein catabolism using 1,2 cyclohexanedione-modified low density lipoprotein. J Lipid Res. 1982 Jan;23(1):92–96. [PubMed] [Google Scholar]
  28. Slater H. R., Packard C. J., Shepherd J. Receptor-independent catabolism of low density lipoprotein. Involvement of the reticuloendothelial system. J Biol Chem. 1982 Jan 10;257(1):307–310. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES