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Journal of Lipid Research, Vol. 46, 1474-1483, July 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Compartmental modeling to quantify -linolenic acid conversion after longer term intake of multiple tracer boluses

Petra L. L. Goyens^*, Mary E. Spilker, Peter L. Zock^,**, Martijn B. Katan^,** and Ronald P. Mensink^1,*,**

^* Department of Human Biology, Maastricht University, Maastricht, The Netherlands
Nuclear Medicine Department, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, The Netherlands
^** Wageningen Center for Food Sciences, Wageningen, The Netherlands

Published, JLR Papers in Press, April 16, 2005. DOI 10.1194/jlr.M400514-JLR200

¹ To whom correspondence should be addressed. e-mail: r.mensink{at}hb.unimaas.nl

To estimate in vivo -linolenic acid (ALA; C18:3n-3) conversion, 29 healthy subjects consumed for 28 days a diet providing 7% of energy from linoleic acid (C18:2n-6) and 0.4% from ALA. On day 19, subjects received a single bolus of 30 mg of uniformly labeled [¹³C]ALA and for the next 8 days 10 mg twice daily. Fasting plasma phospholipid concentrations of ¹²C- and ¹³C-labeled ALA, eicosapentaenoic acid (EPA; C20:5n-3), docosapentaenoic acid (DPA; C22:5n-3), and docosahexaenoic acid (DHA; C22:6n-3) were determined on days 19, 21, 23, 26, 27, and 28. To estimate hepatic conversion of n-3 fatty acids, a tracer model was developed based on the averaged ¹³C data of the participants. A similar tracee model was solved using the averaged ¹²C values, the kinetic parameters derived from the tracer model, and mean ALA consumption. ALA incorporation into plasma phospholipids was estimated by solving both models simultaneously. It was found that nearly 7% of dietary ALA was incorporated into plasma phospholipids. From this pool, 99.8% was converted into EPA and 1% was converted into DPA and subsequently into DHA.

The limited incorporation of dietary ALA into the hepatic phospholipid pool contributes to the low hepatic conversion of ALA into EPA. A low conversion of ALA-derived EPA into DPA might be an additional obstacle for DHA synthesis.

Abbreviations: ALA, -linolenic acid (C18:3n-3); AUC, area under the curve; CE, cholesteryl ester; DHA, docosahexaenoic acid (C22:6n-3); DPA, docosapentaenoic acid (C22:5n-3); En%, percent of energy; EPA, eicosapentaenoic acid (C20:5n-3); FAME, fatty acid methyl ester; LCPUFA, long-chain polyunsaturated fatty acid; TG, triacylglycerol; [U-¹³C]ALA, uniformly labeled [¹³C]-linolenic acid

Supplementary key words desaturation • elongation • metabolism • stable isotopes • human

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