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.

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 x 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.