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

Miki Igarashi,Kaizong Ma,Lisa Chang,Jane M Bell,Stanley I Rapoport

doi:10.1194/jlr.m800093-jlr200

Miki Igarashi, Kaizong Ma + Show 3 more

Open Access

https://doi.org/10.1194/jlr.m800093-jlr200

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Abstract

The extent to which the heart can convert alpha-linolenic acid (alpha-LNA, 18:3n-3) to longer chain n-3 PUFAs is not known. Conversion rates can be measured in vivo using radiolabeled alpha-LNA and a kinetic fatty acid model. [1-(14)C]alpha-LNA was infused intravenously for 5 min in unanesthetized rats that had been fed an n-3 PUFA-adequate [4.6% alpha-LNA, no docosahexaenoic acid (DHA, 22:6n-3)] or n-3 PUFA-deficient diet (0.2% alpha-LNA, nor DHA) for 15 weeks after weaning. Arterial plasma was sampled, as was the heart after high-energy microwaving. Rates of conversion of alpha-LNA to longer chain n-3 PUFAs were low, and DHA was not synthesized at all in the heart. Most alpha-LNA within the heart had been beta-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 Delta6 and Delta5, but elongase-2 mRNA could not be detected. In summary, the rat heart does not synthesize DHA from alpha-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.

Highlights

The extent to which the heart can convert alinolenic acid (a-LNA, 18:3n-3) to longer chain n-3 PUFAs is not known
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be converted from shorter chain a-linolenic acid (a-LNA, 18:3n3), which is enriched in plant oils, by serial steps of desaturation, elongation, and b-oxidation [14,15,16,17,18,19,20]
Using our kinetic method and model, we showed in unanesthetized rats that rates of conversion of a-LNA to DHA were higher in liver than in brain, and that n-3 dietary deprivation could further increase the liver but not brain rates, in relation to elevated expression of requisite desaturases and elongases [21,22,23]

Summary

Introduction

The extent to which the heart can convert alinolenic acid (a-LNA, 18:3n-3) to longer chain n-3 PUFAs is not known. Using our kinetic method and model, we showed in unanesthetized rats that rates of conversion of a-LNA to DHA were higher in liver than in brain, and that n-3 dietary deprivation could further increase the liver but not brain rates, in relation to elevated expression of requisite desaturases and elongases [21,22,23]. These enzymes include D5 and D6 desaturases and elongases-2 and -5.

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