title: Apolipoprotein B-100 kinetics in visceral obesity: associations with plasma apolipoprotein C-III concentration.
abstract: Obesity is strongly associated with dyslipidemia, which may account for the associated increased risk of atherosclerosis and coronary disease. We aimed to test the hypothesis that kinetics of hepatic apolipoprotein B-100 (apoB) metabolism are disturbed in men with visceral obesity and to examine whether these kinetic defects are associated with elevated plasma concentration of apolipoprotein C-III (apoC-III). Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) apoB kinetics were measured in 48 viscerally obese men and 10 age-matched normolipidemic lean men using an intravenous bolus injection of d(3)-leucine. ApoB isotopic enrichment was measured using gas chromatography-mass spectrometry (GCMS). Kinetic parameters were derived using a multicompartmental model (Simulation, Analysis, and Modeling Software II [SAAM-II]). Compared with controls, obese subjects had significantly elevated plasma concentrations of plasma triglycerides, cholesterol, LDL-cholesterol, VLDL-apoB, IDL-apoB, LDL-apoB, apoC-III, insulin, and lathosterol (P <.01). VLDL-apoB secretion rate was significantly higher (P =.034) in obese than control subjects; the fractional catabolic rates (FCRs) of IDL-apoB and LDL-apoB (P <.01) and percent conversion of VLDL-apoB to LDL-apoB (P <.02) were also significantly lower in obese subjects. However, the decreased VLDL-apoB FCR was not significantly different from the lean group. In the obese group, plasma concentration of apoC-III was significantly and positively associated with VLDL-apoB secretion rate and inversely with VLDL-apoB FCR and percent conversion of VLDL to LDL. In multiple regression analysis, plasma apoC-III concentration was independently and significantly correlated with the secretion rate of VLDL-apoB (regression coefficient [SE] 0.511 [0.03], P =.001) and with the percent conversion of VLDL-apoB to LDL-apoB (-0.408 [0.01], P =.004). Our findings suggest that plasma lipid and lipoprotein abnormalities in visceral obesity may be due to a combination of overproduction of VLDL-apoB particles and decreased catabolism of apoB containing particles. Elevated plasma apoC-III concentration is also a feature of dyslipidemia in obesity that contributes to the kinetic defects in apoB metabolism.
authors.affiliation: Department of Medicine, University of Western Australia and the Western Australian Institute for Medical Research, Royal Perth Hospital, Perth, Australia.
authors.forename: Dick C
authors.initials: DC
authors.lastname: Chan
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.forename: Trevor G
authors.initials: TG
authors.lastname: Redgrave
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
mesh_terms: D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000378:metabolism*; D001056:Apolipoproteins C / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007333:Insulin Resistance; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D012044:Regression Analysis
chemical_list: D053299:Apolipoprotein B-100; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D005230:Fatty Acids, Nonesterified; D008055:Lipids