Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1979 Jun;63(6):1262–1273. doi: 10.1172/JCI109421

Kinetic model for production and metabolism of very low density lipoprotein triglycerides. Evidence for a slow production pathway and results for normolipidemic subjects.

L A Zech, S M Grundy, D Steinberg, M Berman
PMCID: PMC372075  PMID: 221537

Abstract

A model for the synthesis and degradation of very low density lipoprotein triglyceride (VLDL-TG) in man is proposed to explain plasma VLDL-TG radioactivity data from studies conducted over a 48-h interval after injection of glycerol labeled with 14C, 3H, or both. The curve describing the radioactivity of plasma VLDL triglycerides reaches a maximum at about 2 h, after which the decay is biphasic in all cases; the late curvature becoming evident only after 8--12 h. To fit the complex curve, it was necessary to postulate two pathways for the incorporation of plasma glycerol into VLDL-TG, one much slower than the other. A process of stepwise delipidation of VLDL in the plasma compartment, previously proposed for VLDL apoprotein models, was also necessary. Predicted VLDL-TG synthesis rates calculated with this model can differ significantly from those based on experiments of shorter duration in which the slow VLDL-TG component is not apparent. The results of these studies strongly support the interpretation that the late, slow component of the VLDL-TG activity curve is predominantly due to the slowly turning-over precursor compartment in the conversion pathway and is not due either to a slow compartment in the labeled precursor, plasma free glycerol, or to an exchange of plasma VLDL-TG with an extravascular compartment. It also cannot, in these studies, be attributed to a slowly turning-over VLDL-TG moiety in the plasma. The model was tested with data from 59 studies including normal subjects and patients with obesity and(or) various forms of hyperlipoproteinemia. Good fits were obtained in all cases, and the estimated parameter values and their uncertainties for 13 normolipemic nonobese subjects are presented. Sensitivty testing was carried out to determine how critical various parameter estimations are to the assumptions introduced in the modeling.

Full text

PDF
1262

Selected References

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

  1. Berman M., Hall M., 3rd, Levy R. I., Eisenberg S., Bilheimer D. W., Phair R. D., Goebel R. H. Metabolsim of apoB and apoC lipoproteins in man: kinetic studies in normal and hyperlipoproteininemic subjects. J Lipid Res. 1978 Jan;19(1):38–56. [PubMed] [Google Scholar]
  2. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  3. Brownell G. L., Berman M., Robertson J. S. Nomenclature for tracer kinetics. Int J Appl Radiat Isot. 1968 Mar;19(3):249–262. doi: 10.1016/0020-708x(68)90022-7. [DOI] [PubMed] [Google Scholar]
  4. Eaton R. P., Berman M., Steinberg D. Kinetic studies of plasma free fatty acid and triglyceride metabolism in man. J Clin Invest. 1969 Aug;48(8):1560–1579. doi: 10.1172/JCI106122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eaton R. P., Crespin S., Kipnis D. M. Incorporation of 75Se-selenomethionine into human apoproteins. III. Kinetic behavior of isotopically labeled plasma apoprotein in man. Diabetes. 1976 Aug;25(8):679–690. doi: 10.2337/diab.25.8.679. [DOI] [PubMed] [Google Scholar]
  6. FARQUHAR J. W., GROSS R. C., WAGNER R. M., REAVEN G. M. VALIDATION OF AN INCOMPLETELY COUPLED TWO-COMPARTMENT NONRECYCLING CATENARY MODEL FOR TURNOVER OF LIVER AND PLASMA TRIGLYCERIDE IN MAN. J Lipid Res. 1965 Jan;6:119–134. [PubMed] [Google Scholar]
  7. Grundy S. M., Mok H. Y., Zech L., Steinberg D., Berman M. Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia. J Clin Invest. 1979 Jun;63(6):1274–1283. doi: 10.1172/JCI109422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Havel R. J., Kane J. P. Quantification of triglyceride transport in blood plasma: a critical analysis. Fed Proc. 1975 Dec;34(13):2250–2257. [PubMed] [Google Scholar]
  10. Higgins J. M., Fielding C. J. Lipoprotein lipase. Mechanism of formation of triglyceride-rich remnant particles from very low density lipoproteins and chylomicrons. Biochemistry. 1975 Jun 3;14(11):2288–2293. doi: 10.1021/bi00682a002. [DOI] [PubMed] [Google Scholar]
  11. Kushwaha R. S., Hazzard W. R., Gagne C., Chait A., Albers J. J. Type III hyperlipoproteinemia: paradoxical hypolipidemic response to estrogen. Ann Intern Med. 1977 Nov;87(5):517–525. doi: 10.7326/0003-4819-87-5-517. [DOI] [PubMed] [Google Scholar]
  12. Malmendier C. L., Delcroix C., Berman M. Interrelations in the oxidative metabolism of free fatty acids, glucose, and glycerol in normal and hyperlipemic patients. A compartmental model. J Clin Invest. 1974 Aug;54(2):461–476. doi: 10.1172/JCI107782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Malmendier C., Berman M. Endogenously labeled low density lipoprotein triglyceride and apoprotein B kinetics. J Lipid Res. 1978 Nov;19(8):978–984. [PubMed] [Google Scholar]
  14. Nikkilä E. A., Kekki M. Measurement of plasma triglyceride turnover in the study of hyperglyceridemia. Scand J Clin Lab Invest. 1971 Apr;27(2):97–104. doi: 10.3109/00365517109080194. [DOI] [PubMed] [Google Scholar]
  15. Nikkilä E. A., Kekki M. Polymorphism of plasma triglyceride kinetics in normal human adult subjects. Acta Med Scand. 1971 Jul-Aug;190(1-2):49–59. doi: 10.1111/j.0954-6820.1971.tb07395.x. [DOI] [PubMed] [Google Scholar]
  16. Pagnan A., Havel R. J., Kane J. P., Kotite L. Characterization of human very low density lipoproteins containing two electrophoretic populations: double pre-beta lipoproteinemia and primary dysbetalipoproteinemia. J Lipid Res. 1977 Sep;18(5):613–622. [PubMed] [Google Scholar]
  17. Phair R. D., Hammond M. G., Bowden J. A., Fried M., Fisher W. R., Berman M. Preliminary model for human lipoprotein metabolism in hyperlipoproteinemia. Fed Proc. 1975 Dec;34(13):2263–2270. [PubMed] [Google Scholar]
  18. Quarfordt S. H., Frank A., Shames D. M., Berman M., Steinberg D. Very low density lipoprotein triglyceride transport in type IV hyperlipoproteinemia and the effects of carbohydrate-rich diets. J Clin Invest. 1970 Dec;49(12):2281–2297. doi: 10.1172/JCI106448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Quarfordt S. H., Levy R. I., Frederickson D. S. The kinetic properties of very low density lipoprotein triglyceride in type 3 hyperlipoproteinemia. Biochim Biophys Acta. 1973 Mar 8;296(3):572–576. doi: 10.1016/0005-2760(73)90117-3. [DOI] [PubMed] [Google Scholar]
  20. Quarfordt S., Levy R. I., Fredrickson D. S. On thelipoprotein abnormality in type 3 hyperlipoproteinemia. J Clin Invest. 1971 Apr;50(4):754–761. doi: 10.1172/JCI106546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Reardon M. F., Fidge N. H., Nestel P. J. Catabolism of very low density lipoprotein B apoprotein in man. J Clin Invest. 1978 Mar;61(3):850–860. doi: 10.1172/JCI108999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reaven G. M., Hill D. B., Gross R. C., Farquhar J. W. Kinetics of triglyceride turnover of very low density lipoproteins of human plasma. J Clin Invest. 1965 Nov;44(11):1826–1833. doi: 10.1172/JCI105290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reichl D., Myant N. B., Pflug J. J. Concentration of lipoproteins containing apolipoprotein B in human peripheral lymph. Biochim Biophys Acta. 1977 Oct 24;489(1):98–105. doi: 10.1016/0005-2760(77)90236-3. [DOI] [PubMed] [Google Scholar]
  24. Reichl D., Myant N. B., Pflug J. J., Rudra D. N. The passage of apoproteins from plasma lipoproteins into the lipoproteins of peripheral lymph in man. Clin Sci Mol Med. 1977 Sep;53(3):221–226. doi: 10.1042/cs0530221. [DOI] [PubMed] [Google Scholar]
  25. Reichl D., Simons L. A., Myant N. B., Pflug J. J., Mills G. L. The lipids and lipoproteins of human peripheral lymph, with observations on the transport of cholesterol from plasma and tissues into lymph. Clin Sci Mol Med. 1973 Sep;45(3):313–329. doi: 10.1042/cs0450313. [DOI] [PubMed] [Google Scholar]
  26. Shames D. M., Frank A., Steinberg D., Berman M. Transport of plasma free fatty acids and triglycerides in man: a theoretical analysis. J Clin Invest. 1970 Dec;49(12):2298–2314. doi: 10.1172/JCI106449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shore V. G., Shore B. Heterogeneity of human plasma very low density lipoproteins. Separation of species differing in protein components. Biochemistry. 1973 Jan 30;12(3):502–507. doi: 10.1021/bi00727a022. [DOI] [PubMed] [Google Scholar]
  28. Streja D., Kallai M. A., Steiner G. The metabolic heterogeneity of human very low density lipoprotein triglyceride. Metabolism. 1977 Dec;26(12):1333–1344. doi: 10.1016/0026-0495(77)90029-4. [DOI] [PubMed] [Google Scholar]

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

RESOURCES