Recycling of Carbon into Lipids Synthesized De Novo Is a Quantitatively Important Pathway of α‐[U‐13C]Linolenate Utilization in the Developing Rat Brain

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Abstract
Docosahexaenoate is important for normal neural development. It can be derived from alpha-linolenate, but carbon from alpha-linolenate is also recycled into de novo lipid synthesis. The objective of this study was to quantify the amount of alpha-linolenate used to produce docosahexaenoate versus lipids synthesized de novo that accumulate in the brain of the developing rat. A physiological dose of carbon-13-labeled alpha-linolenate was injected into the stomachs of mother-reared 6-day-old rat pups. Total lipids of brain, liver, and gut were extracted from rats killed 3 h to 30 days after dosing. Carbon-13 enrichment was determined by isotope ratio mass spectrometry. Carbon-13-enriched alpha-linolenate was not detected in the brain at any time point, and its levels in liver and gut exceeded detection limits at most time points, so tracer mass was quantified mainly for three end products--docosahexaenoate, palmitate, and cholesterol. Carbon-13-enriched cholesterol, palmitate, docosalphahexaenoate, and water-soluble metabolites were detected in brain, liver, and gut Enrichment (in micrograms of carbon-13 per organ) in brain cholesterol exceeded that in brain docosahexaenoate by four- to 16-fold over the duration of the study. Enrichment in brain palmitate exceeded that in brain docosahexaenoate by three- to 30-fold over the first 8 days of the study. These results indicate that carbon from alpha-linolenate is not exclusively conserved for synthesis of longer n-3 polyunsaturates but is a readily accessible carbon source for de novo lipogenesis during early brain development in the suckling rat. Owing to a high rate of beta-oxidation and carbon recycling, dependence on alpha-linolenate as the sole source of docosahexaenoate may incur a potential risk of providing insufficient docosahexaenoate for the developing brain.

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