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.