Original Article

Apolipoprotein B metabolism and the distribution of VLDL and LDL subfractions

Correspondence to: C. J. Packard

Apolipoprotein B (apoB) metabolism was investigated in 20 men with plasma triglyceride 0.66;–2.40 mmol/l and plasma cholesterol 3.95;–6.95 mmol/l. Kinetics of VLDL₁ (S_f 60;–400), VLDL₂ (S_f 20;–60), IDL (S_f 12;–20), and LDL (S_f 0;–12) apoB were analyzed using a trideuterated leucine tracer and a multicompartmental model which allowed input into each fraction. VLDL₁ apoB production varied widely (from 5.4 to 26.6 mg/kg/d) as did VLDL₂ apoB production (from 0.18 to 8.4 mg/kg/d) but the two were not correlated. IDL plus LDL apoB direct production accounted for up to half of total apoB production and was inversely related to plasma triglyceride (r = -0.54, P = 0.009). Percent of direct apoB production into the IDL/LDL density range (r = 0.50, P < 0.02) was positively related to the LDL apoB fractional catabolic rate (FCR). Plasma triglyceride in these subjects was determined principally by VLDL₁ and VLDL₂ apoB fractional transfer rates (FTR), i.e., lipolysis. IDL apoB concentration was regulated mainly by the IDL to LDL FTR (r = -0.71, P < 0.0001). LDL apoB concentration correlated with VLDL₂ apoB production (r = 0.48, P = 0.018) and the LDL FCR (r = -0.77, P < 0.001) but not with VLDL₁, IDL, or LDL apoB production. Subjects with predominantly small, dense LDL (pattern B) had lower VLDL₁ and VLDL₂ apoB FTRs, higher VLDL₂ apoB production, and a lower LDL apoB FCR than those with large LDL (pattern A).

Thus, the metabolic conditions that favored appearance of small, dense LDL were diminished lipolysis of VLDL, resulting in a raised plasma triglyceride above the putative threshold of 1.5 mmol/l, and a prolonged residence time for LDL. This latter condition presumably permitted sufficient time for the processes of lipid exchange and lipolysis to generate small LDL particles.—Packard, C. J., T. Demant, J. P. Stewart, D. Bedford, M. J. Caslake, G. Schwertfeger, A. Bedynek, J. Shepherd, and D. Seidel. Apolipoprotein B metabolism and the distribution of VLDL and LDL subfractions. J. Lipid Res. 2000. 41: 305;–317.

Supplementary key words: stable isotopes, multicompartmental modelling, synthesis, catabolism, mass spectrometry, small dense LDL

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. W. Castellani, C. N. Nguyen, S. Charugundla, M. M. Weinstein, C. X. Doan, W. S. Blaner, N. Wongsiriroj, and A. J. Lusis Apolipoprotein AII Is a Regulator of Very Low Density Lipoprotein Metabolism and Insulin Resistance J. Biol. Chem., April 25, 2008; 283(17): 11633 - 11644. [Abstract] [Full Text] [PDF]

				T. W.K. Ng, G. F. Watts, P. H. R. Barrett, K.-A. Rye, and D. C. Chan Effect of Weight Loss on LDL and HDL Kinetics in the Metabolic Syndrome: Associations with changes in plasma retinol-binding protein-4 and adiponectin levels Diabetes Care, November 1, 2007; 30(11): 2945 - 2950. [Abstract] [Full Text] [PDF]

				I. A. R. Al-Shayji, J. M. R. Gill, J. Cooney, S. Siddiqui, and M. J. Caslake Development of a novel method to determine very low density lipoprotein kinetics J. Lipid Res., September 1, 2007; 48(9): 2086 - 2095. [Abstract] [Full Text] [PDF]

				F. Basso, L. A. Freeman, C. Ko, C. Joyce, M. J. Amar, R. D. Shamburek, T. Tansey, F. Thomas, J. Wu, B. Paigen, et al. Hepatic ABCG5/G8 overexpression reduces apoB-lipoproteins and atherosclerosis when cholesterol absorption is inhibited J. Lipid Res., January 1, 2007; 48(1): 114 - 126. [Abstract] [Full Text] [PDF]

				K. G. Parhofer and P. H. R. Barrett Thematic review series: Patient-Oriented Research. What we have learned about VLDL and LDL metabolism from human kinetics studies J. Lipid Res., August 1, 2006; 47(8): 1620 - 1630. [Abstract] [Full Text] [PDF]

				B. Lundahl, C. Skoglund-Andersson, M. Caslake, D. Bedford, P. Stewart, A. Hamsten, C. J. Packard, and F. Karpe Microsomal triglyceride transfer protein -493T variant reduces IDL plus LDL apoB production and the plasma concentration of large LDL particles Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E739 - E745. [Abstract] [Full Text] [PDF]

				E. R Christ, M. H Cummings, M. Stolinski, N. Jackson, P. J Lumb, A. S Wierzbicki, P. H Sonksen, D. L Russell-Jones, and A M. Umpleby Low-density lipoprotein apolipoprotein B100 turnover in hypopituitary patients with GH deficiency: a stable isotope study. Eur. J. Endocrinol., March 1, 2006; 154(3): 459 - 466. [Abstract] [Full Text] [PDF]

				L. C. Gormsen, M. D. Jensen, and S. Nielsen Measuring VLDL-triglyceride turnover in humans using ex vivo-prepared VLDL tracer J. Lipid Res., January 1, 2006; 47(1): 99 - 106. [Abstract] [Full Text] [PDF]

				K. Ikewaki, J. R. Schaefer, M. E. Frischmann, K. Okubo, T. Hosoya, S. Mochizuki, B. Dieplinger, E. Trenkwalder, H. Schweer, F. Kronenberg, et al. Delayed In Vivo Catabolism of Intermediate-Density Lipoprotein and Low-Density Lipoprotein in Hemodialysis Patients as Potential Cause of Premature Atherosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2615 - 2622. [Abstract] [Full Text] [PDF]

				I. S. Young Lipids for Psychiatrists - an overview J Psychopharmacol, November 1, 2005; 19(6_suppl): 66 - 75. [Abstract] [PDF]

				R. M. Krauss Dietary and Genetic Probes of Atherogenic Dyslipidemia Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2265 - 2272. [Abstract] [Full Text] [PDF]

				M. Adiels, J. Boren, M. J. Caslake, P. Stewart, A. Soro, J. Westerbacka, B. Wennberg, S.-O. Olofsson, C. Packard, and M.-R. Taskinen Overproduction of VLDL1 Driven by Hyperglycemia Is a Dominant Feature of Diabetic Dyslipidemia Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1697 - 1703. [Abstract] [Full Text] [PDF]

				G D Kolovou, K K Anagnostopoulou, and D V Cokkinos Pathophysiology of dyslipidaemia in the metabolic syndrome Postgrad. Med. J., June 1, 2005; 81(956): 358 - 366. [Abstract] [Full Text] [PDF]

				M. Adiels, C. Packard, M. J. Caslake, P. Stewart, A. Soro, J. Westerbacka, B. Wennberg, S.-O. Olofsson, M.-R. Taskinen, and J. Boren A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions J. Lipid Res., January 1, 2005; 46(1): 58 - 67. [Abstract] [Full Text] [PDF]

				C. C. Schwartz, J. M. VandenBroek, and P. S. Cooper Lipoprotein cholesteryl ester production, transfer, and output in vivo in humans J. Lipid Res., September 1, 2004; 45(9): 1594 - 1607. [Abstract] [Full Text] [PDF]

				H. C. Geiss, S. Bremer, P. H. R. Barrett, C. Otto, and K. G. Parhofer In vivo metabolism of LDL subfractions in patients with heterozygous FH on statin therapy: rebound analysis of LDL subfractions after LDL apheresis J. Lipid Res., August 1, 2004; 45(8): 1459 - 1467. [Abstract] [Full Text] [PDF]

				R. Mar, P. Pajukanta, H. Allayee, M. Groenendijk, G. Dallinga-Thie, R. M. Krauss, J. S. Sinsheimer, R. M. Cantor, T. W.A. de Bruin, and A. J. Lusis Association of the APOLIPOPROTEIN A1/C3/A4/A5 Gene Cluster With Triglyceride Levels and LDL Particle Size in Familial Combined Hyperlipidemia Circ. Res., April 16, 2004; 94(7): 993 - 999. [Abstract] [Full Text] [PDF]

				E. R. Christ, M. H. Cummings, N. Jackson, M. Stolinski, P. J. Lumb, A. S. Wierzbicki, P. H. Sonksen, D. L. Russell-Jones, and A. M. Umpleby Effects of Growth Hormone (GH) Replacement Therapy on Low-Density Lipoprotein Apolipoprotein B100 Kinetics in Adult Patients with GH Deficiency: A Stable Isotope Study J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1801 - 1807. [Abstract] [Full Text] [PDF]

				C. Phillips, K. Mullan, D. Owens, and G.H. Tomkin Microsomal triglyceride transfer protein polymorphisms and lipoprotein levels in type 2 diabetes QJM, April 1, 2004; 97(4): 211 - 218. [Abstract] [Full Text] [PDF]

				C.C. Shoulders, E.L. Jones, and R.P. Naoumova Genetics of familial combined hyperlipidemia and risk of coronary heart disease Hum. Mol. Genet., April 1, 2004; 13(90001): R149 - 160. [Abstract] [Full Text] [PDF]

				S. Desroches, J.-F. Mauger, L. M. Ausman, A. H. Lichtenstein, and B. Lamarche Soy Protein Favorably Affects LDL Size Independently of Isoflavones in Hypercholesterolemic Men and Women J. Nutr., March 1, 2004; 134(3): 574 - 579. [Abstract] [Full Text] [PDF]

				S. Bilz, S. Wagner, M. Schmitz, A. Bedynek, U. Keller, and T. Demant Effects of atorvastatin versus fenofibrate on apoB-100 and apoA-I kinetics in mixed hyperlipidemia J. Lipid Res., January 1, 2004; 45(1): 174 - 185. [Abstract] [Full Text] [PDF]

				F. M. Sacks and H. Campos Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4525 - 4532. [Full Text] [PDF]

				W. R. Archer, B. Lamarche, A. C. St-Pierre, J.-F. Mauger, O. Deriaz, N. Landry, L. Corneau, J.-P. Despres, J. Bergeron, P. Couture, et al. High Carbohydrate and High Monounsaturated Fatty Acid Diets Similarly Affect LDL Electrophoretic Characteristics in Men Who Are Losing Weight J. Nutr., October 1, 2003; 133(10): 3124 - 3129. [Abstract] [Full Text] [PDF]

				J. M. Gill, J. C Brown, M. J Caslake, D. M Wright, J. Cooney, D. Bedford, D. A Hughes, J. C Stanley, and C. J Packard Effects of dietary monounsaturated fatty acids on lipoprotein concentrations, compositions, and subfraction distributions and on VLDL apolipoprotein B kinetics: dose-dependent effects on LDL Am. J. Clinical Nutrition, July 1, 2003; 78(1): 47 - 56. [Abstract] [Full Text] [PDF]

				B. Mittendorfer, B. W Patterson, and S. Klein Effect of sex and obesity on basal VLDL-triacylglycerol kinetics Am. J. Clinical Nutrition, March 1, 2003; 77(3): 573 - 579. [Abstract] [Full Text] [PDF]

				N. Landry, N. Bergeron, R. Archer, P. Samson, L. Corneau, J. Bergeron, and O. Deriaz Whole-body fat oxidation rate and plasma triacylglycerol concentrations in men consuming an ad libitum high-carbohydrate or low-carbohydrate diet Am. J. Clinical Nutrition, March 1, 2003; 77(3): 580 - 586. [Abstract] [Full Text] [PDF]

				K. K. Berneis and R. M. Krauss Metabolic origins and clinical significance of LDL heterogeneity J. Lipid Res., September 1, 2002; 43(9): 1363 - 1379. [Abstract] [Full Text] [PDF]

				J. Vakkilainen, M. Jauhiainen, K. Ylitalo, I. O. Nuotio, J. S. A. Viikari, C. Ehnholm, and M.-R. Taskinen LDL particle size in familial combined hyperlipidemia: effects of serum lipids, lipoprotein-modifying enzymes, and lipid transfer proteins J. Lipid Res., April 1, 2002; 43(4): 598 - 603. [Abstract] [Full Text] [PDF]

				D. Plonne, H.-P. Schulze, U. Kahlert, K. Meltke, H. Seidolt, A. J. Bennett, I. J. Cartwright, J. A. Higgins, U. Till, and R. Dargel Postnatal development of hepatocellular apolipoprotein B assembly and secretion in the rat J. Lipid Res., November 1, 2001; 42(11): 1865 - 1878. [Abstract] [Full Text] [PDF]

				S. V. Gupta and P. Khosla Palmitic and Stearic Acids Similarly Affect Plasma Lipoprotein Metabolism in Cynomolgus Monkeys Fed Diets with Adequate Levels of Linoleic Acid J. Nutr., August 1, 2001; 131(8): 2115 - 2120. [Abstract] [Full Text] [PDF]

				J. Q. Purnell, S. E. Kahn, R. S. Schwartz, and J. D. Brunzell Relationship of Insulin Sensitivity and ApoB Levels to Intra-abdominal Fat in Subjects With Familial Combined Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., April 1, 2001; 21(4): 567 - 572. [Abstract] [Full Text] [PDF]

				B. Teusink, A. R. Mensenkamp, H. van der Boom, F. Kuipers, K. W. van Dijk, and L. M. Havekes Stimulation of the in Vivo Production of Very Low Density Lipoproteins by Apolipoprotein E Is Independent of the Presence of the Low Density Lipoprotein Receptor J. Biol. Chem., October 26, 2001; 276(44): 40693 - 40697. [Abstract] [Full Text] [PDF]