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Originally published In Press as doi:10.1194/jlr.M700369-JLR200 on September 17, 2007

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Journal of Lipid Research, Vol. 48, 2709-2724, December 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Whole body distribution of deuterated linoleic and {alpha}-linolenic acids and their metabolites in the rat

Yu Hong Lin and Norman Salem, Jr.1

Section of Nutritional Neuroscience, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9410

Published, JLR Papers in Press, September 17, 2007.

1 To whom correspondence should be addressed. e-mail: nsalem{at}niaaa.nih.gov

Little is known about the uptake or metabolism of essential fatty acids (EFAs) in various mammalian organs. Thus, the distribution of deuterated {alpha}-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) and their metabolites was studied using a stable isotope tracer technique. Rats were orally administered a single dose of a mixture (20 mg each) of ethyl D5-18:3n-3 and D5-18:2n-6, and 25 tissues per animal were analyzed for D5-labeled PUFAs at 4, 8, 24, 96, 168, 240, 360, and 600 h after dosing. Plasma, stomach, and spleen contained the highest concentrations of labeled precursors at the earliest time points, whereas other internal organs and red blood cells reached their maximal concentrations at 8 h. The time-course data were consistent with liver metabolism of EFAs, but local metabolism in other tissues could not be ruled out. Brain, spinal cord, heart, testis, and eye accumulated docosahexaenoic acid with time, whereas skin accumulated mainly 20:4n-6. On average, ~16–18% of the D5-18:3n-3 and D5-18:2n-6 initial dosage was eventually accumulated in tissues, principally in adipose, skin, and muscle. Approximately 6.0% of D5-18:3n-3 and 2.6% of D5-18:2n-6 were elongated/desaturated and stored, mainly in muscle, adipose, and the carcass. The remaining 78% of both precursors was apparently catabolized or excreted.

Supplementary key words docosahexaenoic acid • arachidonic acid • polyunsaturated fatty acid • fatty acid metabolism • stable isotope • gas liquid chromatography-mass spectrometry • essential fatty acid

Abbreviations: BHT, butylated hydroxytoluene; Cmax, maximal concentration; Dmax, maximal amount; EFA, essential fatty acid; GC-MS, gas liquid chromatography-mass spectrometry; GI, gastrointestinal; PFB, pentafluorobenzyl; RBC, red blood cell


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