What we have learned about VLDL and LDL metabolism from human kinetic studies

Klaus G. Parhofer and P Hugh R. Barrett

Medical Dpt. II, Grosshadern, Munich 81377

Corresponding Author: Klaus.Parhofer{at}med.uni-muenchen.de

Lipoprotein metabolism is the result of a complex network of many individual components. Abnormal lipoprotein concentrations can result from changes in production, conversion or catabolism of lipoprotein particles. Studies in hypo- and hyperlipoproteinemia have elucidated the processes that control VLDL secretion as well as VLDL and LDL catabolism. In this manuscript we review the current knowledge regarding apoB metabolism focussing on selected clinically relevant conditions. In hypobetalipoproteinemia due to truncations in apoB, the rate of secretion is closely linked to the length of apoB. On the other hand, in patients with the metabolic syndrome it appears that substrate, in the form of free fatty acids, coupled to the state of insulin resistance can induce hypersecretion of VLDL apoB. Studies in patients with familial hypercholesterolemia, familial defective apoB and mutant forms of PCSK9 show that mutations in the LDL receptor, the ligand for the receptor, or an intracellular chaperone for the receptor are the most important determinants in regulating LDL catabolism. This review also demonstrates the variance of results within similar, or even the same, phenotypic conditions. This underscores the sensitivity of metabolic studies to methodological aspects and thus the importance of the inclusion of adequate controls in studies.

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

This article has been cited by other articles:

L. S. Kumpula, S. M. Makela, V.-P. Makinen, A. Karjalainen, J. M. Liinamaa, K. Kaski, M. J. Savolainen, M. L. Hannuksela, and M. Ala-Korpela
Characterization of metabolic interrelationships and in silico phenotyping of lipoprotein particles using self-organizing maps
J. Lipid Res., February 1, 2010; 51(2): 431 - 439.
[Abstract] [Full Text] [PDF]

M. Adiels, S.-O. Olofsson, M.-R. Taskinen, and J. Boren
Overproduction of Very Low-Density Lipoproteins Is the Hallmark of the Dyslipidemia in the Metabolic Syndrome
Arterioscler Thromb Vasc Biol, July 1, 2008; 28(7): 1225 - 1236.
[Abstract] [Full Text] [PDF]

M. Pan, V. Maitin, S. Parathath, U. Andreo, S. X. Lin, C. St. Germain, Z. Yao, F. R. Maxfield, K. J. Williams, and E. A. Fisher
Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality control
PNAS, April 15, 2008; 105(15): 5862 - 5867.
[Abstract] [Full Text] [PDF]

D. E. Telford, B. G. Sutherland, J. Y. Edwards, J. D. Andrews, P. H. R. Barrett, and M. W. Huff
The molecular mechanisms underlying the reduction of LDL apoB-100 by ezetimibe plus simvastatin
J. Lipid Res., March 1, 2007; 48(3): 699 - 708.
[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]

R. Ramakrishnan
Studying apolipoprotein turnover with stable isotope tracers: correct analysis is by modeling enrichments
J. Lipid Res., December 1, 2006; 47(12): 2738 - 2753.
[Abstract] [Full Text] [PDF]

P. H. R. Barrett, D. C. Chan, and G. F. Watts
Thematic review series: Patient-Oriented Research. Design and analysis of lipoprotein tracer kinetics studies in humans
J. Lipid Res., August 1, 2006; 47(8): 1607 - 1619.
[Abstract] [Full Text] [PDF]