文章基本信息

标题：Quantifying cholesterol synthesis in vivo using 2H2O: enabling back-to-back studies in the same subject
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作者：Stephen F. Previs ; Ablatt Mahsut ; Alison Kulick 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：2011
卷号：52
期号：7
页码：1420-1428
DOI：10.1194/jlr.D014993
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The advantages of using ²H₂O to quantify cholesterol synthesis include i ) homogeneous precursor labeling, ii ) incorporation of ²H via multiple pathways, and iii ) the ability to perform long-term studies in free-living subjects. However, there are two concerns. First, the t_1/2 of tracer in body water presents a challenge when there is a need to acutely replicate measurements in the same subject. Second, assumptions are made regarding the number of hydrogens ( n ) that are incorporated during de novo synthesis. Our primary objective was to determine whether a step-based approach could be used to repeatedly study cholesterol synthesis a subject. We observed comparable changes in the ²H-labeling of plasma water and total plasma cholesterol in African-Green monkeys that received five oral doses of ²H₂O, each dose separated by one week. Similar rates of cholesterol synthesis were estimated when comparing data in the group over the different weeks, but better reproducibility was observed when comparing replicate determinations of cholesterol synthesis in the same nonhuman primate during the respective dosing periods. Our secondary objective was to determine whether n depends on nutritional status in vivo; we observed n of ∼25 and ∼27 in mice fed a high-carbohydrate (HC) versus carbohydrate-free (CF) diet, respectively. We conclude that it is possible to acutely repeat studies of cholesterol synthesis using ²H₂O and that n is relatively constant.
关键词：stable isotopes ; mass spectrometry ; kinetic biomarker ; dyslipidemia ; cardiovascular disease