Document Detail


The use of stable-isotopically labeled oleic acid to interrogate lipid assembly in vivo: assessing pharmacological effects in preclinical species.
MedLine Citation:
PMID:  21415123     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The use of stable labeled substrates and analysis by mass spectrometry has provided substantial insight into rates of synthesis, disposition and utilization of lipids in vivo. The information to be gained from such studies is of particular benefit to therapeutic research where the underlying causes of disease may be related to the production and utilization of lipids. When studying biology through the use of isotope tracers, care must be exercised in interpreting the data to ensure that any response observed can truly be interpreted as biological and not as an artifact of the experimental design or a dilutional effect on the isotope. In this manuscript, we have studied the effects of dosing route and tracer concentration on the mass isotopomer distribution profile as well as the action of selective inhibitors of microsomal triglyceride transfer protein (MTP) in mice and diacylglycerol acyltransferase 1 (DGAT1) in non human primates using a stable labeled approach. Subjects were treated with inhibitor and subsequently given a dose of universally 13C-labeled oleic acid. Samples were analyzed using a rapid LC-MS technique, allowing the effects of the intervention on the assembly and disposition of triglycerides, cholesteryl esters and phospholipids to be determined in a single 3 minute run from just 10 μL of plasma.
Authors:
David G McLaren; Timothy He; Sheng-Ping Wang; Vivienne Mendoza; Raymond Rosa; Karen Gagen; Gowri Bhat; Kithsiri Herath; Paul L Miller; Sloan Stribling; Andrew Taggart; Jason Imbriglio; Jinqi Liu; Dunlu Chen; Shirly Pinto; James M Balkovec; Robert J Devita; Donald J Marsh; Jose M Castro-Perez; Alison Strack; Douglas G Johns; Stephen F Previs; Brian K Hubbard; Thomas P Roddy
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-17
Journal Detail:
Title:  Journal of lipid research     Volume:  -     ISSN:  0022-2275     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Merck Research Laboratories, United States.
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