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:  MEDLINE    
Abstract/OtherAbstract:
The use of stable isotopically labeled substrates and analysis by mass spectrometry have 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. We 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 tri-glyceride transfer protein (MTP) in mice and diacylglycerol acyltransferase 1 (DGAT1) in nonhuman primates, using a stable-isotopically labeled approach. Subjects were treated with inhibitor and subsequently given a dose of uniformly 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 min 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:  2011-03-17
Journal Detail:
Title:  Journal of lipid research     Volume:  52     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-16     Completed Date:  2011-09-19     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1150-61     Citation Subset:  IM    
Affiliation:
Merck Research Laboratories, Merck & Co., Inc. Rahway, NJ, USA. David_McLaren@merck.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Carrier Proteins / antagonists & inhibitors,  metabolism*
Cercopithecus aethiops
Cholesterol Esters / blood*
Chromatography, Liquid
Diacylglycerol O-Acyltransferase / metabolism*
Drug Administration Routes
Drug Evaluation, Preclinical / methods
Enzyme Inhibitors / pharmacology
Female
Isotope Labeling / methods
Isotopes / analysis,  blood
Lipid Metabolism*
Lipoproteins / blood*
Male
Mass Spectrometry
Mice
Mice, Inbred C57BL
Oleic Acid* / metabolism,  pharmacology
Triglycerides / blood*
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Cholesterol Esters; 0/Enzyme Inhibitors; 0/Isotopes; 0/Lipoproteins; 0/Triglycerides; 0/microsomal triglyceride transfer protein; 112-80-1/Oleic Acid; EC 2.3.1.20/Diacylglycerol O-Acyltransferase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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