文章基本信息

标题：The use of stable-isotopically labeled oleic acid to interrogate lipid assembly in vivo: assessing pharmacological effects in preclinical species
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作者：David G. McLaren ; Timothy He ; Sheng-Ping Wang 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：6
页码：1150-1161
DOI：10.1194/jlr.M011049
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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 triglyceride 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.
关键词：cholesteryl ester ; diacylglycerol acyltransferase ; fatty acid ; liquid chromatography-mass spectrometry ; mass isotopomer distribution analysis ; microsomal triglyceride transfer protein ; nonhuman primate ; phosphatidylcholine ; stable isotope tracer ; triglycerides