title: Inter-relationships between proprotein convertase subtilisin/kexin type 9, apolipoprotein C-III and plasma apolipoprotein B-48 transport in obese subjects: a stable isotope study in the postprandial state.
abstract: Postprandial lipaemia, due to elevated plasma apolipoprotein (apo) B-48 concentrations, contributes to increased cardiovascular (CV) risk in obesity. Proprotein convertase subtilisin/kexin type 9 (PCSK9) and apoC-III may play a role in regulating triacylglycerol-rich lipoprotein (TRL)-apoB-48 metabolism. We investigated the associations between plasma PCSK9 and apoC-III concentrations and the kinetics of apoB-48 in obese subjects. Seventeen obese subjects were given an oral fat load. ApoB-48 tracer/tracee ratios were measured after an intravenous 2H3-leucine administration using GC-MS. Kinetic parameters, including secretion and fractional catabolic rates (FCRs), were derived using a multi-compartmental model. Plasma PCSK9 and apoC-III concentrations were significantly and positively (P<0.05 in all) associated with the total area-under-curve (AUC) and incremental AUC for apoB-48 and inversely with TRL-apoB-48 FCR. Plasma PCSK9 and apoC-III concentrations were not correlated (P>0.05 in all) with basal secretion or the number of TRL-apoB-48 secreted over the postprandial period. In the stepwise regression analysis, plasma PCSK9 was the best predictor of the total and incremental AUCs for plasma apoB-48 and the FCR of TRL-apoB-48. The association between plasma PCSK9 and apoC-III and TRL-apoB-48 FCR remained significant (P<0.05 in all) after adjusting for age, homoeostasis model assessment (HOMA) score, hepatic lipase or lipoprotein lipase (LPL). In a multiple regression model, 31% of variance in TRL-apoB-48 FCR was accounted for by plasma PCSK9 and apoC-III concentrations (adjusted R2=0.306, P<0.05). However, their associations with TRL-apoB-48 FCR were not independent of each other. Our results suggest that the catabolism of TRL-apoB-48 in the postprandial state may be co-ordinated by PCSK9 and apoC-III in obese individuals.
authors.affiliation: *School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Dick C
authors.initials: DC
authors.lastname: Chan
authors.affiliation: *School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Annette T Y
authors.initials: AT
authors.lastname: Wong
authors.affiliation: *School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.affiliation: *School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
authors.affiliation: *School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D000368:Aged; D053283:Apolipoprotein B-48 / Q000097:blood*; D053305:Apolipoprotein C-III / Q000097:blood* / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D003903:Deuterium; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000097:blood* / Q000503:physiopathology; D019518:Postprandial Period / Q000502:physiology*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood* / Q000502:physiology; D012697:Serine Endopeptidases / Q000097:blood* / Q000502:physiology
chemical_list: D053283:Apolipoprotein B-48; D053305:Apolipoprotein C-III; D004041:Dietary Fats; D008074:Lipoproteins; D003903:Deuterium; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases