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Plasma Apolipoprotein C-III Transport in Centrally Obese Men: Associations with Very Low-Density Lipoprotein Apolipoprotein B and High-Density Lipoprotein Apolipoprotein A-I Metabolism

Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6847, Australia

Address all correspondence and requests for reprints to: Professor Hugh Barrett, School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, GPO Box X2213, Perth, Western Australia 6847, Australia. E-mail: hugh.barrett{at}uwa.edu.au.

Context: Apolipoprotein (apo) C-III is associated with hypertriglyceridemia and progression of cardiovascular disease. Plasma apoC-III is elevated in centrally obese men, and we hypothesized that the kinetics of apoC-III are disturbed in these subjects.

Objective: We developed a compartmental model to determine very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) apoC-III metabolic parameters in centrally obese men and investigated the associations with VLDL-apoB and HDL-apoA-I kinetics.

Study Design: Apolipoprotein kinetics was determined using stable isotope techniques and compartmental modelling in 39 centrally obese and 12 nonobese men.

Results: Compared with nonobese subjects, centrally obese subjects had increased plasma apoC-III concentration (160 ± 5 mg/liter vs. 103 ± 9 mg/liter, P < 0.001), reflecting increased concentrations of both VLDL-apoC-III and HDL-apoC-III. These related to increased production rate (PR) of VLDL-apoC-III (2.12 ± 0.14 vs. 1.56 ± 0.29 mg/kg·d, P < 0.05) and reduced fractional catabolic rate (FCR) of both VLDL- and HDL-apoC-III (0.70 ± 0.02 pools/d vs. 0.82 ± 0.05 pools/d, P < 0.05). In centrally obese men, VLDL-apoC-III concentration was significantly (P < 0.05) associated with VLDL-apoB concentration and PR as well as HDL-apoA-I FCR and PR and inversely with VLDL-apoB FCR. HDL-apoC-III concentration was significantly (P < 0.05) associated with the concentrations of both VLDL-apoB and HDL-apoA-I, the FCR, and the PR of HDL-apoA-I and inversely with the VLDL-apoB FCR. In multiple regression analysis, both VLDL-apoC-III and HDL-apoC-III concentrations were significantly associated with HDL-apoA-I FCR.

Conclusions: In centrally obese men, elevated VLDL-apoC-III and HDL-apoC-III concentrations are a consequence of elevated production and decreased catabolism of VLDL-apoC-III and reduced catabolism of HDL-apoC-III, respectively. These defects are associated with disturbances in VLDL-apoB and HDL-apoA-I metabolism.

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