Where Does the Developing Brain Obtain Its Docosahexaenoic Acid? Relative Contributions of Dietary α-Linolenic Acid, Docosahexaenoic Acid, and Body Stores in the Developing Rat

Abstract

Docosahexaenoic acid (DHA), a 22-carbon, highly unsaturated, n-3 fatty acid, is important for optimal nervous system function. In this study, designed to quantify how preformed dietary DHA regulates metabolic pathways in vivo, 8-d-old rat pups were divided into four groups and fed artificial rat milk diets. One group was fed formula with deuterium-labeled LNA (d5-LNA) as the only source of n-3 fatty acids, and a second group was fed formula that contained d5-LNA and unlabeled DHA. Two additional groups were dam-reared to permit analysis of fatty acyl pool sizes at postnatal days 8 and 28. The dams were fed a diet that contained 3% unlabeled LNA. DHA in brain and liver was analyzed. Our study demonstrated that preformed DHA in the diet markedly decreased the amount of biosynthesized DHA that accumulated in the brain and the liver. Surprisingly, 40% of the DHA that was newly acquired during this period in the "LNA" group was unlabeled. Because there were no unlabeled n-3 fatty acids in this diet, this DHA must have been derived from body stores of n-3 fatty acids. Thus, body stores can be a significant source of brain DHA in animals that are fed LNA as the only source of n-3 fatty acids. Abbreviations AA, arachidonic acid DHA, docosahexaenoic acid d5-DHA, deuterium-labeled docosahexaenoic acid d5-LNA, deuterium labeled ␣-linolenic acid DPAn-6, docosapentaenoic acid EE, ethyl ester EPA, eicosapentaenoic acid GC, gas chromatography LCP, long-chain polyunsaturate LNA, ␣-linolenic acid MS, mass spectrometry Docosahexaenoic acid (DHA) is a 22-carbon, highly unsaturated, n-3 fatty acid that accumulates in high concentrations in the brain and the retina. It is known that DHA is important for optimal nervous system function as significant deficiency states are associated with decreased behavioral function in animal models (1-8). N-3 fatty acids are essential nutrients for mammals, that is, they cannot be synthesized de novo. However, longer chain n-3 fatty acids such as DHA can be biosynthesized in mammals from n-3 fatty acid precursors such as the 18-carbon n-3 fatty acid ␣-linolenic acid (LNA) (9 -13).An important question for essential fatty acid nutrition has been whether preformed dietary DHA is required or needs can be met with its precursor LNA. Although breast milk always contains DHA (14), until 2002, no infant formula that contained DHA was available in North America as n-3 fatty acids were supplied only in the form of LNA.Whether it is reasonable to expect metabolism of LNA to supply all of the DHA needed for brain and other organ growth remains unclear. Data from previous tracer studies show a marked neural tissue preference for preformed DHA over metabolized LNA during development (15,16). Furthermore, animals that ingest diets with high levels of LNA are unable to reach brain DHA levels of animals that ingest .This study therefore was designed to quantify the amount of brain and liver DHA derived from biosynthesis when preformed DHA was or was not available in the diet. It has been suggested that liver micro...

Whole body distribution of deuterated linoleic and α-linolenic acids and their metabolites in the rat

“…The observation of slightly greater levels of 2 H 5 -22:5n-3 and much higher levels of 2 H 5 -22:6n-3 indicates that (1) shorter chain metabolites were very rapidly metabolized to their C22 products, (2) the primary accretion mechanism for 2 H 5 -22:6n-3 was the uptake of preformed molecules from the circulation, or (3) 18:3n-3 and 20:5n-3 are somehow excluded from many phospholipids and are then b-oxidized. The second conclusion is consistent with other studies (26,(41)(42)(43), although it has been proposed that 2 H 5 -22:5n-3 may also be exported from the liver and taken up into the brain (44).…”

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

“…However, both pathways consume carbon from ␣-linolenate so this comparison does provide a reference point from which the impact of dietary or metabolic manipulation on relative synthesis of docosahexaenoate can be evaluated. The brain has a high requirement for docosahexaenoate but not for other n-3 PUFA, so the fact that 13 C incorporation into lipid products of recycling from ␣-linolenate normally exceeds by several fold ␣-linolenate conversion to docosahexaenoate supports other studies showing that incorporation of preformed (consumed) rather than endogenously synthesized docosahexaenoate is likely to be an important way for the brain to obtain docosahexaenoate (18,19). Why carbon recycling occurs so actively in the suckling period and in the face of high demand for docosahexaenoate is still unclear and will require further investigation.…”

N-3 Fatty Acid Deficiency Induced by a Modified Artificial Rearing Method Leads to Poorer Performance in Spatial Learning Tasks

“…When the brain growth spurt (54) occurs in the absence of dietary n-3 fatty acids, the lack of DHA supply results in a marked loss of brain DHA. Recent studies have shown that most of the brain DHA is supplied by preformed DHA when available in the diet (55). In this study, biosynthesis from LNA is an insignificant source of brain DHA because it has been largely eliminated from the diet (Tables 1 and 3) and circulation (56).…”