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Les données de consommation en acides gras polyinsaturés (AGPI) de la femme allaitante sont rares bien qu’essentielles pour évaluer le niveau d’apport en acides gras du nourrisson et éventuellement orienter la mère vers une alimentation adaptée voire vers une supplémentation en acides gras essentiels. Les données INCA 2 concernant les femmes allaitantes ont été combinées aux données de composition nutritionnelle des aliments de la base de données Ciqual 2013 pour évaluer leurs apports en acides gras. Bien qu’il s’agisse d’un échantillon limité d’individus enquêtés il y a 12 ans, ces données restent malgré tout intéressantes à analyser et à comparer aux recommandations actuelles de l’Anses. Elles montrent que la consommation en AGPI n-3 n’est pas suffisante au regard des recommandations. Par ailleurs, il a été démontré que la composition en acides gras du lait maternel est un marqueur reconnu de la consommation des lipides alimentaires et un bon reflet du niveau de consommation des AGPI n-6 et n-3. Or, les données épidémiologiques relatives à la quantité et à la qualité des lipides consommés en France sont rares. Dans le cadre de différentes études cliniques conduites sur le lait maternel, l’ITERG a pu ainsi estimer l’évolution des habitudes alimentaires des Français depuis près de 17 ans. Un travail de synthèse a repris l’ensemble des données acquises au cours de 4 études cliniques menées entre 1997 et 2014. Cette synthèse a mis en évidence une évolution positive des proportions en AGPI n-3 en 17 ans (1997–2014). Toutefois, les proportions d’acide alpha-linolénique (ALA) et d’acide docosahexaénoïque (DHA) dans le lait maternel restent en deçà des recommandations nutritionnelles pour le nouveau-né.

During the perinatal period, maternal dietary polyunsaturated fatty acids (PUFA) ensure optimal infant development. Observational studies on cognitive and visual development reported that a specific deficit intake in n-3 PUFA in pregnant women was associated with a reduction in visual acuity in 2-months-old infants. Moreover, a low docosahexaenoic acid (DHA) content associated with a high level of n-6 PUFA in breast milk was negatively associated with the degree of cognitive development in 6-years-old children. As regards to adipose tissue development, only observational human data agree with the hypothesis that excessive dietary intakes of n-6 PUFA compared with n-3 PUFA could promote the development of adipose tissue and obesity. With regard to immune system development, observational and clinical studies suggest that long-chain n-3 PUFA consumption during pregnancy may prevent the incidence of allergic diseases in children. Lastly, specific association between the maternal ingestion of food groups and the infant health has been studied mainly on allergic outcomes (fish, dairy products). Nutritional recommendations for PUFA intake in pregnant and lactating women were mainly based on brain development data, corresponding to breast milk levels of 10% of total fatty acids for linoleic acid, 1.5% for α-linolenic acid and 0.4% for DHA.

Recommendations for infant formulas (IF) had been established on the basis of human breast milk composition, still considered as “the gold standard”. Historically, till the 20th century, cow milk-based formulas have been used to feed infants when breast feeding was not possible. Later, infant formulas based on cow’s milk proteins but only vegetable oils blends as lipid source became the usual rule in most countries. However, considering “the gold standard”, a lot of changes occurred since the sixties that considerably modified lipid composition of human breast milk which is correlated to the diet of the mothers, who increased their consumption of n-6PUFA to replace saturated fat considered as proatherogenic. This introduced an imbalance in the ratio of linoleic/alpha-linolenic acids (18:2n-6/18:3n-3), limiting the bioconversion to long-chain-n-3 docosahexaenoic acid (DHA, 22:6n-3). Compared to pure vegetable blends and following the usual recommendations for IF, linoleic (LA 15% of total fatty acids), alpha-linolenic acids (ALA 1.5%) and LA/ALA ratio (10), the use of dairy fat blend was beneficial in terms of brain DHA accretion in young rats and a further increase of brain DHA was obtained by using pure dairy fat (LA 2%, ALA 0.8%, LA/ALA 2.3). Cow’s milk presents naturally some similarities (lipid quality, cholesterol, globule structure…) with human breast milk and cannot be compared to pure vegetable blends. Utilization of dairy fat in infant formula should be reconsidered, as well as the absolute amount of polyunsaturated LA and ALA: at least a reduction of LA for IF as well as for lactating women to improve breast milk quality.

The rapid growth of the neonate requires a high intake of both energy and lipids. Fatty acids may play an important role in the brain development and in the etiology of several disorders in children and adults. Most of infant formulas currently marketed have a fatty acid profile globally mimicking that of the ‘‘gold reference’’, the human milk. However several issues remain to be improved to optimizing their lipid status: Structure of the fat globule. Fat globules of human milk differ from those of infant formulas by their larger size and the presence of a phospholipid membrane. Recent experimental data in animal models of infant nutrition suggest that this specificity of natural milk may prevent the development of the metabolic syndrome. In addition, palmitic acid is mainly esterified in the sn-2 position of triglycerides in human milk, versus in the sn-1 and sn-3 positions in infant formulas. This sn-2 esterification may favor the intestinal absorption of other fatty acids and then their tissue bioavailability ; PUFA metabolism. The exclusive use of vegetable oils in infant formulas has increased the content of both polyunsaturated fatty acid precursors (linoleic and a-linolenic acids). However, several studies have led to the observation that high PUFA contents in formulas may reduce the incorporation of docosahexaenoic acid in tissues ; N-6 PUFA intake and obesity. In western countries, the increasing incidence of obesity has coincided with the gradual increase of n-6 PUFA from food and, incidentally, from an n-6/n-3 imbalance. Animal studies have recently shown that high linoleic acid intake and high ratio of linoleic to a-linolenic acids during the perinatal period activate the adipose tissue growth in the young and adult. To date, two observational studies confirm the existence of a link between the n-6/n-3 ratio in cord or the n-6 content in maternal plasma and adiposity in 3-7 years old infants.

The content of docosahexaenoic acid (DHA) in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1) a lower brain glucose utilization, 2) a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3) a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.

Background: Long-chain polyunsaturated fatty acids (LC-PUFA) are nutritionally important constituents of breast milk to support normal growth, immune function and central nervous system development of newborn infants. Both linoleic acid (18:2 n-6; LA) and alpha-linolenic acid (18:3 n-3; ALA), the essential fatty acids, precursors of n-6 and n-3 LC-PUFA, are also present in breast milk. Although the total amount of fat in human milk is fairly constant, the fatty acid composition can vary substantially depending on the diet of the mother. Large variations in the LA, ALA and DHA (22:6 n-3) contents are observed among countries. As reported by previous studies (1993-2001), the ALA consumption of the French population was 2-3 times lower than the recommended value. Since this period, the food industry offers more food products enriched in n-3 fatty acids. Objective: The present study aimed to investigate whether current recommendations and improved n-3 PUFA content of food products comply with the actual breast-milk PUFA composition. For this purpose, the PUFA content of a large number of human milk samples collected in 2007 in different French regions were compared with previous data obtained in studies conducted in the nineties years (1993-1998). Moreover, this study aimed to confirm expected reduction of the trans fatty acid (TFA) intake resulting from decreased level of TFA in margarine and other dietary fats during the same period. Study design and methods: Mature (postpartum day ≥ 30) human milk samples (n = 145) were provided in 2007 by eight French regional human milk banks (Bordeaux : n = 20; Dijon: n = 21; Ile-de-France: n = 18; Lyon: n = 20; Montpellier: n = 18; Nantes: n = 21; St Etienne: n = 6; Tours: n = 21), from healthy women volunteers with no particular health history. The fatty acid composition of breast milk was analysed by high-resolution gas-liquid chromatography. Statistical analysis was performed with Kruskall Wallis and Mann and Whitney U tests (p < 0.05). Results: Fatty acid composition of human milk samples did not differ significantly among the eight French regions. The proportions of saturated fatty acids were relatively similar (means ranging from 44.9% to 48.7% of total fatty acids). Monounsaturated fatty acids also varied little, from 36.9% to 39.7%. Total n-6 and n-3 PUFA accounted for 12.5%-15.2%, with an n-6/n-3 PUFA ratio close to 10, similar among the collect centers. Considering the overall results, LA represented between 10.4% and 12.7%, and ALA varied from 0.72% to 0.95%. Comparison of our results to previous data (1993-1998) showed opposite changes for LA and ALA. During the last decade, the LA level has decreased by 17%, whereas the ALA level has increased by 45%, and hence in 2007, the LA/ ALA ratio was close to 14 versus 24 in 1993-1998. The LC-PUFA content remained unchanged. Concerning total TFA, their content was lower (– 37%; p < 0.0001) in 2007 than in 1997, respectively 1.3% and 2.1% of total fatty acids of breast milk. Conclusion: Basing on the PUFA composition of human milk, this large French study shows favourable changes in consumption of both omega-6 and omega-3 fatty acid precursors, and in TFA, in the course of last decade.

Docosahexaenoic acid (DHA, 22:6n-3) in membrane phospholipids originates from dietary intake of preformed DHA and from conversion of its essential precursor α-linolenic acid (ALA, 18:3n-3). Cultured cells, especially nervous cells, are increasingly used to explore the uptake, metabolism and gene transcription effects of n-3 fatty acids, raising the question of the specific metabolic fate of different fatty acids and of the physiological relevance of their concentrations in the culture medium. This paper reports experimental data that 1) compare the dose-dependent incorporation of preformed DHA into the ethanolamine phosphoglycerolipids (EPG) of neural and cerebral endothelial cells in culture with that of the developing rat brain, 2) evaluate the pathway of DHA synthesis from ALA, eicosapentaenoic acid (EPA, 20:5n-3) or n-3 docosapentaenoic acid (DPA, 22:5n-3) in a model of neuronal cells, the SH-5YSY human neuroblastoma cells, and 3) characterize in these cells the mRNA expression profile of genes involved in the fatty acid metabolism. The incorporation of preformed DHA in EPG followed, both in vivo and in vitro, a dose-response curve from which two parameters were drawn: the DHAmax, i.e. the plateau-value of the linearized dose-response curve (expressed in weight % of total fatty acids), and the DHA50, the concentration of DHA in the diet or in the culture medium corresponding to an incorporation of DHA in EPG equal to one-half the DHAmax. The ratio of DHAmax to DHA50 reflects the propensity (so-called the ‘avidity’ for DHA) of cells or tissues to incorporate the exogenous DHA. The DHAmax and the DHAmax/DHA50 ratio values of SH-SY5Y cells and of rat brain endothelial cells in culture were compared to those of the frontal cortex and hippocampus of rats chronically deficient in n-3 fatty acids and supplemented with preformed DHA. The same DHAmax/DHA50 ratio values were found in SH-SY5Y (5.2) cells and in rat brain areas (5.1-5.7) when the DHA doses were expressed in lmol DHA/liter of culture medium and in lmol DHA/10 g diet, respectively. The SH-SY5Y cells were able to produce neoformed EPA, DPA and DHA from supplemental ALA. The incorporation of neoformed EPA and DPA in EPG followed a dose-response saturating curve, while that of DHA was bell-shaped. The different pattern of neoformed DPA and neoformed DHA suggests that the conversion pathway was limited at the terminal step of DHA synthesis. The mRNA profile showed that two enzymes of the peroxisomal b-oxidation system, the L- and D-bifunctional proteins, were expressed at lower levels than those of the endoplasmic reticulum pathway (Δ6-desaturase). These data show that incorporation of preformed DHA in cultured neuroblastoma cells match physiological values, indicating that DHA uptake, acyl-CoA activation, and phospholipid acyltransferases are active. However, the synthesis and incorporation of newly formed DHA in SH-SY5Y cells responds to a critical concentration-window of precursors which could originate from the low basal expression level of peroxisomal enzymes.

The very high enrichment of the nervous system in the polyunsaturated fatty acids, arachidonic (AA, 20: 4n-6) and docosahexaenoic acids (DHA, 22: 6n-3), is dependant of the dietary availability of their respective precursors, linoleic (18: 2n-6) and_-linolenic acids (18: 3n-3). Inadequate amounts of DHA in brain membranes have been linked to a wide variety of abnormalities ranging from visual acuity and learning irregularities, to psychopathologies. However, the molecular mechanisms involved remain unknown. Several years ago, we hypothesized that a modification of DHA contents of neuronal membranes by dietary modulation could change the neurotransmission function and then underlie inappropriate behavioural response. We showed that, in parallel to a severe loss of brain DHA concomitant to a compensatory substitution by 22:5n-6, the dietary lack of α-linolenic acid during development induced important changes in the release of neurotransmitters (dopamine, serotonin, acetylcholine) in cerebral areas specifically involved in learning, memory and reward processes. Data suggested alteration of presynaptic storage process and dysregulations of reciprocal functional interactions between monoaminergic and cholinergic pathways. Moreover, we showed that recovery of these neurochemical changes was possible when the deficient diet was switched to a diet balanced in n-3 and n-6 PUFA before weaning. The next step is to understand the mechanism involved. Particularly, we focus on the study of the metabolic cooperation between the endothelial cell, the astrocyte and the neuron which regulate synaptic transmission.These works could contribute to the understanding of the link between some neuropsychiatric disorders and the metabolism of n-3 PUFA, through their action on neurotransmission.

Long chain polyunsaturated fatty acids (PUFAs), particularly arachidonic acid and docosahexaenoic acid (DHA), are integral components of neural membrane phospholipids. DHA deficiency is associated with behavioural and neurophysiological disorders. A deficiency of DHA markedly affects neurotransmission, membrane-bound proteins, ion channel activities and synaptic plasticity, and the supplementation restores neurotransmission. Although the molecular mechanism of DHA involvement remains unknown, more and more data demonstrate its implication in various cellular activities contributing to regulation of neurotransmission. Since recent studies have provided evidence that n-3 deficiency altered neurogenesis in embryonic brain, the question of lasting effects on neural function can be addressed.

The 7th congress was organized by the International Society For the Study of Fatty Acids and Lipids (ISSFAL) in Cairns (Australia) from 23 to 28 July 2006. It joined more than 400 delegates from 35 countries. The meeting included a plenary program, with 25 conferences and selected short communications, and 32 concurrent sessions in which around 300 free communications were presented (oral + posters). The primary themes explored several areas of research on lipids, fatty acids, metabolism and cerebral functions (3 sessions and 4 plenary conferences) with respect to maternal and infant health (3 sessions), ageing (1 session) and Alzheimer disease (1 session), omega-3 fatty acids and mental health (1 session), PUFA metabolism (3 sessions), the impact of dietary omega-3 and trans fatty acids on several pathologies such as obesity (1 session), cardiovascular disease and the metabolic syndrome (4 sessions and 3 plenary conferences), diabetes (1 session), cancer (1 session) and osteoporosis (1 session). Lastly, several concurrent sessions focused on methodological aspects for implementing new dietary sources of fatty acids (4 sessions).

Polyunsaturated fatty acids (PUFAs) are essential nutrients for mammals and the human species, and belong to either of two distinct and not interconvertible series, omega 6 and omega 3. The metabolic precursors of these two series, linoleic and α-linolenic acids respectively, are the dietary essential fatty acids. These two fatty acids, once absorbed, lead to the specific synthesis and incorporation in practically all cell membranes of long-chain active PUFA derivatives such as arachidonic acid for the omega 6 series and eicosapentaenoic and docosahexaenoic acids for the omega 3 series. Long-chain PUFA affect many physiological functions because they are essential factors in many cellular functions by regulating physical properties of membranes, eicosanoid signalling and gene expression of encoding enzymes of triglyceride storage and fatty acid oxidation. The consumption of omega 6 and omega 3 fatty acids in equilibrated proportions could be crucial in the regulation of cellular physiology and in the prevention of pathologies such as cardiovascular, autoimmune and inflammatory diseases, diabetes and obesity, certain neuropsychiatric affections, etc. Indeed, the dietary intake of omega 3 fatty acid (α-linolenate and also docosahexaenoate) are crucial parameters in the development of retinal and neural function in the newborn infant. On the other hand, a high ratio of omega6/omega 3 fatty acids in cell membranes due to an excessive consumption of omega 6 fatty acids and a relative omega 3 fatty acid deficiency, may promote the pathogenesis of several diseases, including cardiovascular diseases, metabolic syndrome, inflammatory disorders and obesity.

Polyunsaturated fatty acids (PUFA) are nutritionally important constituents of breast milk to support normal growth, immune function and central nervous system development of newborn infants. Both linoleic acid (18:2 n-6; LA) and alpha-linolenic acid (18:3 n-3 ; ALA), the essential fatty acids, precursors of n-6 and n-3 long-chain PUFA. LA and LNA contents in human milk reflect differences in dietary fats consumed by the mothers, including those consumed during several months (long term impact). The composition of breast milk from this point of view is a reliable biological marker of the level of habitual consumption of PUFAs in different populations. An increase of LA content for the 1950-1990 period, without any change of LNA content, has been reported in breast milk of women living in western countries, reflecting changes in LA intake by the mother.

The altered neuron activity of rats deficient in (n-3) PUFAs may be due in part to a decrease in brain glucose utilization and glucose transport. We measured the glucose transporter protein GLUT1 isoforms at the blood-brain barrier (55-kDa) and in astrocytes (45-kDa) by Western immunoblotting and their mRNA by real time RT-PCR analysis in the cerebral cortex of adult male rats fed diets lacking (n-3) fatty acids (1st generation). The neuron glucose transporter GLUT3 was also assayed. The fatty acids in the phosphatidylcholine (PC), ethanolamine phosphoglycerolipid (EPG), and phosphatidylserine (PS) fractions of isolated microvessels and homogenates of the cerebral cortex were determined. The levels of (n-6) PUFAs [mainly arachidonic acid, 20:4(n-6)] in the phospholipid fractions of microvessels were higher and the levels of (n-3) PUFAs [mainly docosahexaenoic acid, 22:6(n-3)] were lower than in cerebral cortex homogenates. The microvessels and cortex of rats fed the (n-3) PUFA-deficient diet had 50% of the control 22:6(n-3) contents; 22:6(n-3) was replaced by 22:5(n-6). The 55-kDa GLUT1 immunoreactivity in (n-3) PUFA-deficient microvessels was decreased (down 25%, P < 0.01), as was the 45 kDa-GLUT1 in the homogenate (down 30%, P < 0.01). But the amount of immunoreactivity of GLUT3 did not change. The amount of GLUT1 mRNA was not affected by the (n-3) PUFA-deficient diet. These results suggest that the decreased glucose utilization in the cerebral cortex of (n-3) PUFA-deficient rats is due to reduced amounts of the 2 isoforms of GLUT1, indicating post-transcriptional regulation of GLUT1 synthesis. KEY WORDS: * astrocytes * microvessels * endothelial cells * glucose transporters * (n-3) fatty acids