This Article Full Text Full Text (PDF) All Versions of this Article: 91/3/973    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ji, J. Articles by Barrett, P. H. R. Search for Related Content PubMed PubMed Citation Articles by Ji, J. Articles by Barrett, P. H. R. Related Collections Diabetes and Insulin Metabolism Lipid

High-Density Lipoprotein (HDL) Transport in the Metabolic Syndrome: Application of a New Model for HDL Particle Kinetics

Lipoprotein Research Unit (J.J., G.F.W., D.C.C., E.M.M.O., P.H.R.B.), School of Medicine and Pharmacology, University of Western Australia, The West Australian Institute for Medical Research, Perth, WA 6847, Australia; GlaxoSmithKline R & D (A.G.J.), King of Prussia, Pennsylvania 19406; Lipid Research Group (K.-A.R.), The Heart Research Institute, Sydney, Australia; Department of Medicine (K.-A.R.), University of Sydney, Sydney, Australia; Department of Medicine (K.-A.R.), University of Melbourne, Melbourne, Australia; and James Lance GlaxoSmithKline Medicines Research Unit (A.P.S.), Prince of Wales Hospital, Sydney, NSW 2052, Australia

Address all correspondence and requests for reprints to: Professor G. F. Watts, School of Medicine and Pharmacology, Royal Perth Hospital, Box X2213 GPO, Perth, WA 6847, Australia. E-mail: gfwatts{at}cyllene.uwa.edu.au.

Context: Reduced high density lipoprotein (HDL) concentration in the metabolic syndrome (MetS) is associated with increased risk of diabetes and cardiovascular disease and is related to defects in the kinetics of HDL apolipoprotein (apo) A-I and A-II.

Objective: The objective of the study was to investigate HDL apoA-I and apoA-II kinetics in nondiabetic men with MetS and lean controls by developing a model that describes the kinetics of lipoprotein (Lp)A-I and LpA-I:A-II particles.

Design: Twenty-three MetS men and 10 age-matched lean controls were investigated. ApoA-I and apoA-II tracer/tracee ratios were studied after iv d₃-leucine administration using gas chromatography mass spectrometry.

Results: Compared with lean subjects, MetS subjects had accelerated catabolism of LpA-I (P < 0.001), LpA-I:A-II (P = 0.005), and apoA-II (P = 0.005); the production rate of LpA-I was also significantly elevated in MetS, so that the dominant changes in plasma concentrations were reduction in LpA-I:A-II (P < 0.001) and apoA-II (P < 0.05). Increased catabolism of LpA-I and LpA-I:A-II was directly related to increased waist circumference, hypertriglyceridemia, low HDL-cholesterol, small HDL particle size, hyperinsulinemia, and low phospholipid transfer protein (PLTP) activity; overproduction of LpA-I was significantly associated with increased waist circumference, insulin resistance, and low PLTP activity.

Conclusions: MetS men exhibit hypercatabolism of the two major HDL lipoprotein particles, LpA-I and LpA-I:A-II, but selective overproduction of LpA-I maintains a normal plasma concentration of LpA-I. These kinetic perturbations are probably related to central obesity, insulin resistance, hypertriglyceridemia, and low plasma PLTP activity.

This article has been cited by other articles:

				E. M. M. Ooi, G. F. Watts, P. J. Nestel, D. Sviridov, A. Hoang, and P. H. R. Barrett Dose-Dependent Regulation of High-Density Lipoprotein Metabolism with Rosuvastatin in the Metabolic Syndrome J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 430 - 437. [Abstract] [Full Text] [PDF]

				R. P F Dullaart, A. K Groen, G. M Dallinga-Thie, R. de Vries, W. J Sluiter, and A. van Tol Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol Eur. J. Endocrinol., January 1, 2008; 158(1): 53 - 60. [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]

				D. C Chan, G. F Watts, M. N Nguyen, and P H. R Barrett Factorial study of the effect of n-3 fatty acid supplementation and atorvastatin on the kinetics of HDL apolipoproteins A-I and A-II in men with abdominal obesity Am. J. Clinical Nutrition, July 1, 2006; 84(1): 37 - 43. [Abstract] [Full Text] [PDF]