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

Postprandial lipaemia, due to elevated plasma apolipoprotein (apo) B-48 concentrations, contributes to increased cardiovascular risk in obesity. Proprotein convertase subtilisin/kexin type 9 (PCSK9) and apoC-III may play a role in regulating 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 intravenous d3-leucine administration using gas chromatography-mass spectrometry. Kinetic parameters, including secretion and fractional catabolic rates (FCR), 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 apoB-48 FCR. Plasma PCSK9 and apoC-III concentrations were not correlated (P>0.05 in all) with basal secretion or number of apoB-48 secreted over the postprandial period. In stepwise regression analysis, plasma PCSK9 was the best predictor of the total and incremental AUCs for plasma apoB-48, and the FCR of apoB-48. The association between plasma PCSK9 and apoC-III and apoB-48 FCR remained significant (P<0.05 in all) after adjusting for age, homeostasis model assessment score (HOMA), hepatic lipase or lipoprotein lipase. In a multiple regression model, 31% of variance in apoB-48 FCR was acco...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research