| Quantifying cholesterol synthesis in vivo using 2H2O: Enabling back-to-back studies in the same subject. | |
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MedLine Citation:
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PMID: 21498887 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 t1/2 of 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. We examined a step-based approach for repeating studies in a subject, African-Green monkeys received five oral doses of 2H2O each separated by one week. Comparable changes in the 2H-labeling of plasma water and total plasma cholesterol were observed during the respective dosing periods. We observed similar rates of cholesterol synthesis 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 non-human primate. In parallel, we determined that the n is independent of nutritional status in vivo; we observed n of ~ 25 and ~ 27 in mice fed high-carbohydrate vs carbohydrate-free diets, respectively. We conclude that it is possible to acutely repeat studies of cholesterol synthesis using 2H2O and that n is relatively constant. |
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Authors:
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Stephen F Previs; Ablatt Mahsut; Alison Kulick; Keiana Dunn; Genevieve Andrews-Kelly; Christopher Johnson; Gowri Bhat; Kithsiri Herath; Paul L Miller; Sheng-Ping Wang; Karim Azer; Jing Xu; Douglas G Johns; Brian K Hubbard; Thomas P Roddy |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-17 |
Journal Detail:
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Title: Journal of lipid research Volume: - ISSN: 0022-2275 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Merck, United States; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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