High-density lipoprotein (HDL) transport in the metabolic syndrome: application of a new model for HDL particle kinetics.
BACKGROUND
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.


METHODS
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.
Ji
Juying
J
Lipoprotein Research Unit, School of Medicine and Pharmacology, Royal Perth Hospital, Box X2213 GPO, Perth, WA 6847, Australia.
Watts
Gerald F
GF
Johnson
Anthony G
AG
Chan
Dick C
DC
Ooi
Esther M M
EM
Rye
Kerry-Anne
KA
Serone
Adrian P
AP
Barrett
P Hugh R
PH
D016632:Apolipoprotein A-I / Q000097:blood* / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000097:blood*; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008954:Models, Biological; D012016:Reference Values
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008075:Lipoproteins, HDL