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

• Published in: Clinical science (1979) Vol. 128; no. 6; pp. 379 - 385
• Main Authors: Chan, Dick C., Wong, Annette T. Y., Pang, Jing, Barrett, P. Hugh R., Watts, Gerald F.
• Format: Journal Article
• Language: English
• Published: England 01.03.2015
• Subjects: Aged; Apolipoprotein B-48 - blood; Apolipoprotein C-III - blood; Apolipoprotein C-III - physiology; Biological Transport - physiology; Deuterium; Dietary Fats - administration & dosage; Female; Humans; Lipoproteins - blood; Male; Middle Aged; Models, Biological; Obesity - blood; Obesity - physiopathology; Postprandial Period - physiology; Proprotein Convertase 9; Proprotein Convertases - blood; Proprotein Convertases - physiology; Serine Endopeptidases - blood; Serine Endopeptidases - physiology
• ISSN: 0143-5221; 1470-8736; 1470-8736
• DOI: 10.1042/CS20140559

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.