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. 1987 Apr;79(4):1110–1119. doi: 10.1172/JCI112926

Different patterns of postprandial lipoprotein metabolism in normal, type IIa, type III, and type IV hyperlipoproteinemic individuals. Effects of treatment with cholestyramine and gemfibrozil.

M S Weintraub, S Eisenberg, J L Breslow
PMCID: PMC424291  PMID: 3470306

Abstract

To study exogenous fat metabolism, we used the vitamin A-fat loading test, which specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). Postprandial RP concentrations were followed in total plasma, and chylomicron (Sf greater than 1,000) and nonchylomicron (Sf less than 1,000) fractions. In normal subjects postprandial lipoproteins were present for more than 14 h, and chylomicron levels correlated inversely with lipoprotein lipase activity and fasting high density lipoprotein (HDL) cholesterol levels and nonchylomicron levels correlated inversely with hepatic triglyceride lipase activity. The main abnormality in type IV patients was a 5.6-fold increase in the chylomicron fraction, whereas in type III patients it was a 6.4-fold increase in nonchylomicrons. Type IIa patients had abnormally low chylomicron fractions. In type IV patients gemfibrozil decreased, whereas in type IIa patients cholestyramine increased the chylomicron fraction 66 and 88%, respectively. This study demonstrates an unexpectedly large magnitude and long duration of postprandial lipemia in normal subjects and patients. These particles are potentially atherogenic, and their role in human atherosclerosis warrants further study.

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Selected References

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

  1. Beil U., Crouse J. R., Einarsson K., Grundy S. M. Effects of interruption of the enterohepatic circulation of bile acids on the transport of very low density-lipoprotein triglycerides. Metabolism. 1982 May;31(5):438–444. doi: 10.1016/0026-0495(82)90231-1. [DOI] [PubMed] [Google Scholar]
  2. Bensadoun A., Kompiang I. P. Role of lipoprotein lipase in plasma triglyceride removal. Fed Proc. 1979 Nov;38(12):2622–2626. [PubMed] [Google Scholar]
  3. Berr F., Eckel R. H., Kern F., Jr Contraceptive steroids increase hepatic uptake of chylomicron remnants in healthy young women. J Lipid Res. 1986 Jun;27(6):645–651. [PubMed] [Google Scholar]
  4. Berr F., Eckel R., Kern F., Jr Plasma decay of chylomicron remnants is not affected by heparin-stimulated plasma lipolytic activity in normal fasting man. J Lipid Res. 1985 Jul;26(7):852–859. [PubMed] [Google Scholar]
  5. Berr F., Kern F., Jr Plasma clearance of chylomicrons labeled with retinyl palmitate in healthy human subjects. J Lipid Res. 1984 Aug;25(8):805–812. [PubMed] [Google Scholar]
  6. Bhattacharya S., Redgrave T. G. The content of apolipoprotein B in chylomicron particles. J Lipid Res. 1981 Jul;22(5):820–828. [PubMed] [Google Scholar]
  7. Blanchette-Mackie E. J., Scow R. O. Sites of lipoprotein lipase activity in adipose tissue perfused with chylomicrons. Electron microscope cytochemical study. J Cell Biol. 1971 Oct;51(1):1–25. doi: 10.1083/jcb.51.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Blomhoff R., Rasmussen M., Nilsson A., Norum K. R., Berg T., Blaner W. S., Kato M., Mertz J. R., Goodman D. S., Eriksson U. Hepatic retinol metabolism. Distribution of retinoids, enzymes, and binding proteins in isolated rat liver cells. J Biol Chem. 1985 Nov 5;260(25):13560–13565. [PubMed] [Google Scholar]
  9. Bond J. H., Jr, Levitt M. D., Prentiss R. Investigation of small bowel transit time in man utilizing pulmonary hydrogen (H2) measurements. J Lab Clin Med. 1975 Apr;85(4):546–555. [PubMed] [Google Scholar]
  10. Breckenridge W. C., Little J. A., Alaupovic P., Wang C. S., Kuksis A., Kakis G., Lindgren F., Gardiner G. Lipoprotein abnormalities associated with a familial deficiency of hepatic lipase. Atherosclerosis. 1982 Nov;45(2):161–179. doi: 10.1016/0021-9150(82)90136-8. [DOI] [PubMed] [Google Scholar]
  11. Carrella M., Cooper A. D. High affinity binding of chylomicron remnants to rat liver plasma membranes. Proc Natl Acad Sci U S A. 1979 Jan;76(1):338–342. doi: 10.1073/pnas.76.1.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chait A., Brunzell J. D., Albers J. J., Hazzard W. R. Type-III Hyperlipoproteinaemia ("remnant removal disease"). Insight into the pathogenetic mechanism. Lancet. 1977 Jun 4;1(8023):1176–1178. doi: 10.1016/s0140-6736(77)92717-9. [DOI] [PubMed] [Google Scholar]
  13. Chait A., Hazzard W. R., Albers J. J., Kushwaha R. P., Brunzell J. D. Impaired very low density lipoprotein and triglyceride removal in broad beta disease: comparison with endogenous hypertriglyceridemia. Metabolism. 1978 Sep;27(9):1055–1066. doi: 10.1016/0026-0495(78)90151-8. [DOI] [PubMed] [Google Scholar]
  14. DOLE V. P., HAMLIN J. T., 3rd Particulate fat in lymph and blood. Physiol Rev. 1962 Oct;42:674–701. doi: 10.1152/physrev.1962.42.4.674. [DOI] [PubMed] [Google Scholar]
  15. Daggy B. P., Bensadoun A. Enrichment of apolipoprotein B-48 in the LDL density class following in vivo inhibition of hepatic lipase. Biochim Biophys Acta. 1986 Jun 27;877(2):252–261. doi: 10.1016/0005-2760(86)90302-4. [DOI] [PubMed] [Google Scholar]
  16. DeRuyter M. G., De Leenheer A. P. Simultaneous determination of retinol and retinyl esters in serum or plasma by reversed-phase high-performance liquid chromatography. Clin Chem. 1978 Nov;24(11):1920–1923. [PubMed] [Google Scholar]
  17. Ehnholm C., Mahley R. W., Chappell D. A., Weisgraber K. H., Ludwig E., Witztum J. L. Role of apolipoprotein E in the lipolytic conversion of beta-very low density lipoproteins to low density lipoproteins in type III hyperlipoproteinemia. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5566–5570. doi: 10.1073/pnas.81.17.5566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Eisenberg S. High density lipoprotein metabolism. J Lipid Res. 1984 Oct;25(10):1017–1058. [PubMed] [Google Scholar]
  19. Fielding C. J., Higgins J. M. Lipoprotein lipase: comparative properties of the membrane-supported and solubilized enzyme species. Biochemistry. 1974 Oct 8;13(21):4324–4330. doi: 10.1021/bi00718a013. [DOI] [PubMed] [Google Scholar]
  20. GOODMAN D. S. The metabolism of chylomicron cholesterol ester in the rat. J Clin Invest. 1962 Oct;41:1886–1896. doi: 10.1172/JCI104645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. GOODMAN D. W., HUANG H. S., SHIRATORI T. TISSUE DISTRIBUTION AND METABOLISM OF NEWLY ABSORBED VITAMIN A IN THE RAT. J Lipid Res. 1965 Jul;6:390–396. [PubMed] [Google Scholar]
  22. Goldberg I. J., Le N. A., Paterniti J. R., Jr, Ginsberg H. N., Lindgren F. T., Brown W. V. Lipoprotein metabolism during acute inhibition of hepatic triglyceride lipase in the cynomolgus monkey. J Clin Invest. 1982 Dec;70(6):1184–1192. doi: 10.1172/JCI110717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Goodman D. S., Blomstrand R., Werner B., Huang H. S., Shiratori T. The intestinal absorption and metabolism of vitamin A and beta-carotene in man. J Clin Invest. 1966 Oct;45(10):1615–1623. doi: 10.1172/JCI105468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Grundy S. M., Mok H. Y. Chylomicron clearance in normal and hyperlipidemic man. Metabolism. 1976 Nov;25(11):1225–1239. doi: 10.1016/s0026-0495(76)80006-6. [DOI] [PubMed] [Google Scholar]
  25. HAVEL R. J. Early effects of fat ingestion on lipids and lipoproteins of serum in man. J Clin Invest. 1957 Jun;36(6 Pt 1):848–854. doi: 10.1172/JCI103491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Havel R. J., Chao Y., Windler E. E., Kotite L., Guo L. S. Isoprotein specificity in the hepatic uptake of apolipoprotein E and the pathogenesis of familial dysbetalipoproteinemia. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4349–4353. doi: 10.1073/pnas.77.7.4349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hazzard W. R., Bierman E. L. Delayed clearance of chylomicron remnants following vitamin-A-containing oral fat loads in broad-beta disease (type III hyperlipoproteinemia). Metabolism. 1976 Jul;25(7):777–801. doi: 10.1016/0026-0495(76)90149-9. [DOI] [PubMed] [Google Scholar]
  28. Hui D. Y., Brecht W. J., Hall E. A., Friedman G., Innerarity T. L., Mahley R. W. Isolation and characterization of the apolipoprotein E receptor from canine and human liver. J Biol Chem. 1986 Mar 25;261(9):4256–4267. [PubMed] [Google Scholar]
  29. Hui D. Y., Innerarity T. L., Mahley R. W. Lipoprotein binding to canine hepatic membranes. Metabolically distinct apo-E and apo-B,E receptors. J Biol Chem. 1981 Jun 10;256(11):5646–5655. [PubMed] [Google Scholar]
  30. Jansen H., van Tol A., Hülsmann W. C. On the metabolic function of heparin-releasable liver lipase. Biochem Biophys Res Commun. 1980 Jan 15;92(1):53–59. doi: 10.1016/0006-291x(80)91518-1. [DOI] [PubMed] [Google Scholar]
  31. KORN E. D. Clearing factor, a heparin-activated lipoprotein lipase. I. Isolation and characterization of the enzyme from normal rat heart. J Biol Chem. 1955 Jul;215(1):1–14. [PubMed] [Google Scholar]
  32. Krauss R. M., Levy R. I., Fredrickson D. S. Selective measurement of two lipase activities in postheparin plasma from normal subjects and patients with hyperlipoproteinemia. J Clin Invest. 1974 Nov;54(5):1107–1124. doi: 10.1172/JCI107855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Manninen V., Mälkönen M., Eisalo A., Virtamo J., Tuomilehto J., Kuusisto P. Gemfibrozil in the treatment of dyslipidaemia. A 5-year follow-up study. Acta Med Scand Suppl. 1982;668:82–87. doi: 10.1111/j.0954-6820.1982.tb08526.x. [DOI] [PubMed] [Google Scholar]
  35. Murase T., Itakura H. Accumulation of intermediate density lipoprotein in plasma after intravenous administration of hepatic triglyceride lipase antibody in rats. Atherosclerosis. 1981 Jun;39(3):293–300. doi: 10.1016/0021-9150(81)90015-0. [DOI] [PubMed] [Google Scholar]
  36. NESTEL P. J., DENBOROUGH M. A., O'DEA J. Disposal of human chylomicrons administered intravenously in ischemic heart disease and essential hyperlipemia. Circ Res. 1962 May;10:786–791. doi: 10.1161/01.res.10.5.786. [DOI] [PubMed] [Google Scholar]
  37. Nicoll A., Lewis B. Evaluation of the roles of lipoprotein lipase and hepatic lipase in lipoprotein metabolism: in vivo and in vitro studies in man. Eur J Clin Invest. 1980 Dec;10(6):487–495. doi: 10.1111/j.1365-2362.1980.tb02090.x. [DOI] [PubMed] [Google Scholar]
  38. Nikkilä E. A., Ylikahri R., Huttunen J. K. Gemfibrozil: effect on serum lipids, lipoproteins, postheparin plasma lipase activities and glucose tolerance in primary hypertriglyceridaemia. Proc R Soc Med. 1976;69 (Suppl 2):58–63. [PMC free article] [PubMed] [Google Scholar]
  39. Olefsky J. M., Crapo P., Reaven G. M. Postprandial plasma triglyceride and cholesterol responses to a low-fat meal. Am J Clin Nutr. 1976 May;29(5):535–539. doi: 10.1093/ajcn/29.5.535. [DOI] [PubMed] [Google Scholar]
  40. Olson J. A. Recent developments in the fat-soluble vitamins. Metabolism and function of vitamin A. Fed Proc. 1969 Sep-Oct;28(5):1670–1677. [PubMed] [Google Scholar]
  41. Olsson A. G., Rössner S., Walldius G., Carlson L. A. Effect of gemfibrozil on lipoprotein concentrations in different types of hyperlipoproteinaemia. Proc R Soc Med. 1976;69 (Suppl 2):28–31. [PMC free article] [PubMed] [Google Scholar]
  42. Patsch J. R., Karlin J. B., Scott L. W., Smith L. C., Gotto A. M., Jr Inverse relationship between blood levels of high density lipoprotein subfraction 2 and magnitude of postprandial lipemia. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1449–1453. doi: 10.1073/pnas.80.5.1449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Read N. W., McFarlane A., Kinsman R. I., Bates T. E., Blackhall N. W., Farrar G. B., Hall J. C., Moss G., Morris A. P., O'Neill B. Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon. Gastroenterology. 1984 Feb;86(2):274–280. [PubMed] [Google Scholar]
  44. Redgrave T. G., Carlson L. A. Changes in plasma very low density and low density lipoprotein content, composition, and size after a fatty meal in normo- and hypertriglyceridemic man. J Lipid Res. 1979 Feb;20(2):217–229. [PubMed] [Google Scholar]
  45. Redgrave T. G. Catabolism of chylomicron triacylglycerol and cholesteryl ester in genetically obese rats. J Lipid Res. 1977 Sep;18(5):604–612. [PubMed] [Google Scholar]
  46. Redgrave T. G. Formation of cholesteryl ester-rich particulate lipid during metabolism of chylomicrons. J Clin Invest. 1970 Mar;49(3):465–471. doi: 10.1172/JCI106255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Ross A. C., Zilversmit D. B. Chylomicron remnant cholesteryl esters as the major constituent of very low density lipoproteins in plasma of cholesterol-fed rabbits. J Lipid Res. 1977 Mar;18(2):169–181. [PubMed] [Google Scholar]
  48. Saku K., Gartside P. S., Hynd B. A., Kashyap M. L. Mechanism of action of gemfibrozil on lipoprotein metabolism. J Clin Invest. 1985 May;75(5):1702–1712. doi: 10.1172/JCI111879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Steender S., Zilversmit D. B. Arterial influx of esterified cholesterol from two plasma lipoprotein fractions and its hydrolysis in vivo in hypercholesterolemic rabbits. Atherosclerosis. 1981 Apr;39(1):97–109. doi: 10.1016/0021-9150(81)90092-7. [DOI] [PubMed] [Google Scholar]
  50. Stender S., Zilversmit D. B. Comparison of cholesteryl ester transfer from chylomicrons and other plasma lipoproteins to aortic intima media of cholesterol-fed rabbits. Arteriosclerosis. 1982 Nov-Dec;2(6):493–499. doi: 10.1161/01.atv.2.6.493. [DOI] [PubMed] [Google Scholar]
  51. Vega G. L., Grundy S. M. Gemfibrozil therapy in primary hypertriglyceridemia associated with coronary heart disease. Effects on metabolism of low-density lipoproteins. JAMA. 1985 Apr 26;253(16):2398–2403. [PubMed] [Google Scholar]
  52. Warnick G. R., Benderson J., Albers J. J. Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. Clin Chem. 1982 Jun;28(6):1379–1388. [PubMed] [Google Scholar]
  53. Wilson D. E., Chan I. F., Ball M. Plasma lipoprotein retinoids after vitamin A feeding in normal man: minimal appearance of retinyl esters among low-density lipoproteins. Metabolism. 1983 May;32(5):514–517. doi: 10.1016/0026-0495(83)90016-1. [DOI] [PubMed] [Google Scholar]
  54. Wilson D. E., Chan I. F., Buchi K. N., Horton S. C. Postchallenge plasma lipoprotein retinoids: chylomicron remnants in endogenous hypertriglyceridemia. Metabolism. 1985 Jun;34(6):551–558. doi: 10.1016/0026-0495(85)90193-3. [DOI] [PubMed] [Google Scholar]
  55. Windler E., Chao Y., Havel R. J. Regulation of the hepatic uptake of triglyceride-rich lipoproteins in the rat. Opposing effects of homologous apolipoprotein E and individual C apoproteins. J Biol Chem. 1980 Sep 10;255(17):8303–8307. [PubMed] [Google Scholar]
  56. Zilversmit D. B. Atherogenesis: a postprandial phenomenon. Circulation. 1979 Sep;60(3):473–485. doi: 10.1161/01.cir.60.3.473. [DOI] [PubMed] [Google Scholar]

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