RECYCLING OF CARBON INTO LIPIDS SYNTHESIZED DE-NOVO IS A QUANTITATIVELY IMPORTANT PATHWAY OF ALPHA-[U-C-13]LINOLENATE UTILIZATION IN THE DEVELOPING RAT-BRAIN

Docosahexaenoate is important for normal neural development. It can be derived from alpha-linolenate, but carbon from alpha-linolenate is al so recycled into de novo lipid synthesis. The objective of this study was to quantify the amount of alpha-linolenate used to produce docosah exaenoate versus lipids synthesized de novo that accumulate in the bra in of the developing rat. A physiological dose of carbon-13-labeled al pha-linolenate was injected into the stomachs of mother-reared B-day-o ld 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 det ermined by isotope ratio mass spectrometry. Carbon-13-enriched alpha-l inolenate was not detected in the brain at any time point, and its lev els in liver and gut exceeded detection limits at most time points, so tracer mass was quantified mainly for three end products-docosahexaen oate, palmitate, and cholesterol, Carbon-13-enriched cholesterol, palm itate, docosahexaenoate, and water-soluble metabolites were detected i n brain, liver, and gut. Enrichment (in micrograms of carbon-13 per or gan) in brain cholesterol exceeded that in brain docosahexaenoate by f our- to 16-fold over the duration of the study. Enrichment in brain pa lmitate exceeded that in brain docosahexaenoate by three- to 30-fold o ver the first 8 days of the study. These results indicate that carbon from alpha-linolenate is not exclusively conserved for synthesis of lo nger n-3 polyunsaturates but is a readily accessible carbon source for de novo lipogenesis during early brain development in the suckling ra t. Owing to a high rate of beta-oxidation and carbon recycling, depend ence on alpha-linolenate as the sole source of docosahexaenoate may in cur a potential risk of providing insufficient docosahexaenoate for th e developing brain.