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Journal of Lipid Research, Vol. 49, 1735-1745, August 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Rat heart cannot synthesize docosahexaenoic acid from circulating -linolenic acid because it lacks elongase-2

Miki Igarashi¹, Kaizong Ma, Lisa Chang, Jane M. Bell and Stanley I. Rapoport

Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892

This research was supported entirely by the Intramural Research Program of the National Institute on Aging.

Published, JLR Papers in Press, May 1, 2008.

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

The extent to which the heart can convert -linolenic acid (-LNA, 18:3n-3) to longer chain n-3 PUFAs is not known. Conversion rates can be measured in vivo using radiolabeled -LNA and a kinetic fatty acid model. [1-¹⁴C]-LNA was infused intravenously for 5 min in unanesthetized rats that had been fed an n-3 PUFA-adequate [4.6% -LNA, no docosahexaenoic acid (DHA, 22:6n-3)] or n-3 PUFA-deficient diet (0.2% -LNA, nor DHA) for 15 weeks after weaning. Arterial plasma was sampled, as was the heart after high-energy microwaving. Rates of conversion of -LNA to longer chain n-3 PUFAs were low, and DHA was not synthesized at all in the heart. Most -LNA within the heart had been β-oxidized. In deprived compared with adequate rats, DHA concentrations in plasma and heart were both reduced by >90%, whereas heart and plasma levels of docosapentaenoic acid (DPAn-6, 22:5n-6) were elevated. Dietary deprivation did not affect cardiac mRNA levels of elongase-5 or desaturases 6 and 5, but elongase-2 mRNA could not be detected. In summary, the rat heart does not synthesize DHA from -LNA, owing to the absence of elongase-2, but must obtain its DHA entirely from plasma. Dietary n-3 PUFA deprivation markedly reduces heart DHA and increases heart DPAn-6, which may make the heart vulnerable to different insults.

Supplementary key words diet • heart • deprivation • elongation • synthesis • n-3 polyunsaturated fatty acids

Abbreviations: AA, arachidonic acid (20:4n-6); CPT, carnitine-o-palmitoyltransferase; DPA, docosapentaenoic acid (22:5); DHA, docosahexaenoic acid (22:6n-3); EPA, eicosapentaenoic acid (20:5n-3); FAME, fatty acid methyl ester; HPLC; high-performance liquid chromatography; LA, linoleic acid (18:2n-6); -LNA, -linolenic acid (18:3n-3)

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