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

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.

Fig. 1

Radioactivity in heart aqueous fraction and lipids in dietary n-3 PUFA-adequate and -deficient rats after intravenous infusion of [1-¹⁴C]α-LNA for 5 min. A: Radioactivity of total lipid and aqueous phases in both groups. B: Radioactivity in individual lipids. TG, triacylglycerol; PL, phospholipid; Chol, cholesterol. Open bars represent the n-3 PUFA-adequate group; closed bars represent the deprived group. Values are means ± SD (n = 10 and 7 in adequate and deficient group, respectively).

Fig. 2

mRNA levels of Δ6 desaturase (A), Δ5 desaturase (B), elongase-5 (C), elongase-2 (D), and acyl-CoA oxidase (E) in heart of rats fed n-3 PUFA-adequate and n-3 PUFA-deficient diets. ND, not detected. Values are means ± SD (n = 10 for each group). ** P < 0.01, differs significantly from mean in adequate group.

Fig. 3

Scheme of plasma-derived α-LNA uptake and metabolic pathways in rat heart as determined following 5 min intravenous infusion of [1-¹⁴C]α-LNA. Heart compartment contents of [1-¹⁴C]α-LNA were calculated by dividing the radioactivity in each compartment by the net total heart radioactivity (excluding unesterified plasma fatty acid radioactivity) and expressing the values as a percentage. The left number in parentheses is for the n-3 PUFA-adequate group, the right for the deprived group. Arrows show metabolic pathways.