文章基本信息

标题：Evaluation of CETP activity in vivo under non-steady-state conditions: influence of anacetrapib on HDL-TG flux
本地全文：下载
作者：David G. McLaren ; Stephen F. Previs ; Robert D. Phair 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2016
卷号：57
期号：3
页码：398-409
DOI：10.1194/jlr.M063842
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Studies in lipoprotein kinetics almost exclusively rely on steady-state approaches to modeling. Herein, we have used a non-steady-state experimental design to examine the role of cholesteryl ester transfer protein (CETP) in mediating HDL-TG flux in vivo in rhesus macaques, and therefore, we developed an alternative strategy to model the data. Two isotopomers ([²H₁₁] and [¹³C₁₈]) of oleic acid were administered (orally and intravenously, respectively) to serve as precursors for labeling TGs in apoB-containing lipoproteins. The flux of a specific TG (52:2) from these donor lipoproteins to HDL was used as the measure of CETP activity; calculations are also presented to estimate total HDL-TG flux. Based on our data, we estimate that the peak total postprandial TG flux to HDL via CETP is ∼13 mg·h⁻¹·kg⁻¹ and show that this transfer was inhibited by 97% following anacetrapib treatment. Collectively, these data demonstrate that HDL TG flux can be used as a measure of CETP activity in vivo. The fact that the donor lipoproteins can be labeled in situ using well-established stable isotope tracer techniques suggests ways to measure this activity for native lipoproteins in free-living subjects under any physiological conditions.
关键词：cholesteryl ester transfer protein ; rhesus macaques ; lipoproteins ; postprandial ; non-steady-state dynamics ; ProcessDB ; high density lipoprotein ; triglyceride