Suckling Rats Actively Recycle Carbon from α-Linolenate into Newly Synthesized Lipids Even During Extreme Dietary Deficiency of n-3 Polyunsaturates

Abstract

Docosahexaenoate is usually considered to be the principal endpoint of ␣-linolenate metabolism in mammals. Nevertheless, several studies over the past 30 y have shown that more carbon from ␣-linolenate is recycled into newly synthesized lipids than is used to make docosahexaenoate. Our objective in this study was to assess carbon recycling from ␣-linolenate in suckling rats made deficient in n-3 polyunsaturated fatty acids (PUFA). Female Long-Evans rats were given a diet deficient in n-3 PUFA at weaning and then bred 8 wk later. Pups from the second generation were nursed by their respective dams and gavaged with 1 mg [U-13 C]-␣-linolenate at 10 d old. Brain and liver were obtained 24 h later, and the fatty acid profiles and 13 C enrichment analyzed. Docosahexaenoate was markedly depleted in brain (Ϫ82%) and liver (Ϫ97%) of the n-3 PUFA-deficient rats. In the controls, 13 C enrichment in products of carbon recycling (cholesterol and fatty acids other than n-3 PUFA) exceeded that in docosahexaenoate by 2.4-fold (liver) and 7.5-fold (brain). n-3 PUFA deficiency reduced the ratio of 13 C enrichment in products of carbon recycling compared with 13 C incorporated into docosahexaenoate by 63% in the brain but not in the liver. Despite severe n-3 PUFA deficiency, carbon recycling still consumed 50% more 13 C from ␣-linolenate than went into docosahexaenoate in the liver and 2.8-fold more in the brain. We conclude that carbon recycling is an integral part of neonatal metabolism of ␣-linolenate and is not simply an overflow pathway arising from excess availability of preformed docosahexaenoate. (Pediatr Res 59: 107-110, 2006)

Rapid de-esterification and loss of eicosapentaenoic acid from rat brain phospholipids: an intracerebroventricular study

“…In accordance with previous reports (Miller et al. 1987; Cunnane et al. 2006), the appearance of de novo synthesized radiolabeled fatty acids, fatty aldehydes, and cholesterol suggests that the brain conserved carbons from fatty acid β‐oxidation.…”

“…Therefore, as expected, ChoGpl and EtnGpl fractions, but not PtdSer and PtdIns, had radiolabeled fatty aldehydes when individual phospholipid fractions were examined (Sun and Horrocks 1968;Diagne et al 1984). In accordance with previous reports (Miller et al 1987;Cunnane et al 2006), the appearance of de novo synthesized radiolabeled fatty acids, fatty aldehydes, and cholesterol suggests that the brain conserved carbons from fatty acid b-oxidation.…”

Markedly raised intake of saturated and monounsaturated fatty acids in rats on a high‐fat ketogenic diet does not inhibit carbon recycling of13C‐α‐linolenate

“…It now seems clear that, under experimental conditions ranging from extreme dietary and tissue depletion of n-3 fatty acids to raised intake and tissue content of saturates and monounsaturates, carbon recycling of ALA is consistently observed (7). The biological significance underlying this quantitatively important pathway remains to be established.…”

“…ALA recycling into de novo lipid products appears to be a preferential pathway of ALA utilization in tissues because it occurs regardless of dietary n-3 PUFA status (7,8). In young rats, ALA recycling into de novo lipid products is not altered by ALA deficiency during early development, a period when the demand for n-3 PUFA is thought to be at its highest (7).…”

“…In young rats, ALA recycling into de novo lipid products is not altered by ALA deficiency during early development, a period when the demand for n-3 PUFA is thought to be at its highest (7). Conversely, adult rats fed a diet enriched with DHA continue to recycle exogenously administered 14 C-ALA into sterols and products of de novo fatty acid synthesis (8).…”