Long-chain polyunsaturated fatty acids in maternal and infant nutrition

Homo sapiens has evolved on a diet rich in alpha-linolenic acid and long chain polyunsaturated fatty acids (LCP). We have, however, gradually changed our diet from about 10,000 years ago and accelerated this change from about 100 to 200 years ago. The many dietary changes, including lower intake of omega3-fatty acids, are related to 'typically Western' diseases. After a brief introduction in essential fatty acids (EFA), LCP and their functions, this contribution discusses our present low status of notably LCPomega3 in the context of our rapidly changing diet within an evolutionary short time frame. It then focuses on the consequences in pregnancy, lactation and neonatal nutrition, as illustrated by some recent data from our group. We discuss the concept of a 'relative' EFA/LCP deficiency in the fetus as the outcome of high transplacental glucose flux. This flux may in the fetus augment de novo synthesis of fatty acids, which not only dilutes transplacentally transported EFA/LCP, but also causes competition of de novo synthesized oleic acid with linoleic acid for delta-6 desaturation. Such conditions were encountered by us in mothers with high body mass indices, diabetes mellitus and preeclampsia. The unifying factor might be compromised glucose homeostasis. In search of the milk arachidonic acid (AA) and docosahexaenoic acid (DHA) contents of our African ancestors, we investigated women in Tanzania with high intakes of freshwater fish as only animal lipid source. These women had milk AA and DHA contents that were well above present recommendations for infant formulae. Both studies stimulate rethinking of 'optimal homeostasis'. Subtle signs of dysbalanced maternal glucose homeostasis may be important and observations from current Western societies may not provide us with an adequate basis for dietary recommendations.     

Effects of postnatal age and diet on the fatty acid composition of plasma lipid fractions in preterm infants

Diet and postnatal age effect the fatty acid composition of plasma and tissue lipids. This work was designed as a transversal study to evaluate the changes in the fatty acid composition of plasma phospholipids, cholesteryl esters, triglycerides and free fatty acids in preterm infants (28-35 weeks gestational age), fed human milk (HM) and milk formula (MF) from birth to 1 month of life. Sixteen blood samples were obtained from cord, and 19 at 6-8 h after birth, 14 at 1 week and 9 at 4 weeks from HM-fed infants and 18 at 1 week and 14 at 4 weeks from MF-fed ones. Groups had similar mean birth weight, gestational age and sex ratio. The MF provided 69 kcal/dl and contained 16% of linoleic acid and 1.3% of alpha-linolenic acid on the total fat. Plasma lipid fractions were extracted and separated by thin-layer chromatography and fatty acid methyl esters were quantitated by gas liquid chromatography. In plasma phospholipids, linoleic acid (18:2 omega 6) continuously increased from birth to 1 month of age, but no changes were seen as related to type of diet; polyunsaturated fatty acids greater than 18 carbon atoms of both the omega 6 and omega 3 series (PUFA omega 6 greater than 18 C and omega 3 greater than 18 C) dropped from birth to 1 week and continued to decrease in MF-fed infants until 1 month; eicosatrienoic (20:3 omega 6), arachidonic (20:4 omega 6) and docosahexaenoic (22:6 omega 3) were the fatty acids implicated. In cholesteryl esters palmitoleic (16:1 omega 7) and oleic (18:1 omega 9) acids decreased from birth to 1 month and linoleic acid increased and arachidonic acid dropped, especially in MF fed infants. In triglycerides, palmitic, palmitoleic and stearic acid (18:0) decreased during the first month of life; oleic acid remained constant and linoleic acid increased in all infants, but arachidonic acid decreased only in those fed formula. Free fatty acids showed a similar behavior in fatty acids and in plasma triglycerides. Preterm neonates seem to have special requirements of long-chain PUFA and adapted MF should contain these fatty acids in similar amounts to those of HM to allow the maintenance of an adequate tissue structure and physiology.     

Phospholipid and triacylglycerol fatty acid content and pattern in the cardiac endothelium of rats depleted in long-chain polyunsaturated omega 3 fatty acids

Rats depleted in long-chain polyunsaturated omega3 fatty acids (omega3-depleted rats) display several features of the metabolic syndrome including hypertension and cardiac hypertrophy. This coincides with alteration of the cardiac muscle phospholipid and triacylglycerol fatty acid content and/or pattern. In the present study, the latter variables were measured in the cardiac endothelium of normal and omega3-depleted rats. Samples derived from four rats each were obtained from 16 female normal fed rats and three groups of 36-40 female fed omega3-depleted rats each aged 8-9, 15-16 and 22-23 weeks. At comparable mean age, the ratio between the square root of the total fatty acid content of phospholipids and cubic root of the total fatty acid content of triacylglycerols was lower in omega3-depleted rats than in control animals. The total fatty acid content of triacylglycerols was inversely related to their relative content in C20:4omega6. Other differences between omega3-depleted rats and control animals consisted in a lower content of long-chain polyunsaturated omega3 fatty acids in both phospholipids and triacylglycerols, higher content of long-chain polyunsaturated omega6 fatty acids in phospholipids, higher activity of delta9-desaturase (C16:0/C16:1omega7 and C18:0/C18:1omega9 ratios) and elongase [(C16:0 + C16:1omega7)/(C18:0 + C18:1omega9) and C20:4omega6/C22:4omega6 ratios], but impaired generation of C22:6omega3 from C22:5omega3 in the former rats. These findings support the view that cardiovascular perturbations previously documented in the omega3-depleted rats may involve impaired heart endothelial function.     

Polyunsaturated fatty acids in maternal plasma and in breast milk

In order to explain processes underlying the transfer of fatty acids from the maternal compartment into human milk, the lipid content and the fatty acid composition of maternal plasma and milk have been analyzed in breastfeeding mothers at 1 day and 3 months of lactation.The rise in milk lipids occurring during the study period was concomitant with a fall in plasma total fat content, mainly due to the decrease of triglycerides. Significant correlations between plasma and milk fatty acids at the two time points were observed only for linoleic (LA, 18:2 n-6) and (alpha;-linolenic acid (alpha LNA, 18:3 n-3), while for arachidonic (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) correlations were found only at one day and 3 months, respectively.These data suggest that levels of the n-6 and n-3 18C polyunsaturated fatty acids in milk are closely dependent on their concentrations in maternal plasma, in turn related with the dietary intake, while the accumulation of AA and DHA in milk is the result of a sequence of transfer and metabolic processes.     

Lower fetal status of docosahexaenoic acid, arachidonic acid and essential fatty acids is associated with less favorable neonatal neurological condition

Long-chain polyunsaturated fatty acids, notably arachidonic (AA) and docosahexaenoic (DHA) acids are abundant in brain and may be conditionally essential in fetal life. We investigated umbilical artery (UA) and vein (UV) fatty acid compositions and early neonatal neurological condition in 317 term infants. Neurological condition was summarized as a clinical classification and a 'neurological optimality score' (NOS). Neurologically abnormal infants (n=27) had lower UV DHA and essential fatty acid (EFA) status. NOS correlated positively with AA (UV), and EFA (UV) and DHA status (UV and UA) and negatively with 18:2omega6 and omega9 (UV), and 20:3omega9, omega7 and C18 trans fatty acids (UV and UA). UV DHA, AA, saturated fatty acids, gestational age and obstetrical optimality score explained 16.2% of the NOS variance. Early postnatal neurological condition seems negatively influenced by lower fetal DHA, AA and EFA status. C18 trans fatty acids and 18:2omega6 may exert negative effects by impairment of LCP status.     

Rapid effects of the intravenous injection of a medium-chain triglyceride: fish oil emulsion on the triglyceride fatty acid pattern of soleus muscle from omega3 fatty acid-depleted rats.

Second generation rats depleted in long-chain polyunsaturated omega3 fatty acids display several features of the metabolic syndrome, including visceral obesity, liver steatosis, insulin resistance, hypertension, and cardiac hypertrophy. In the framework of an extensive study on such metabolic, hormonal and functional perturbations, the phospholipid fatty acid pattern and ex vivo metabolism of D-glucose were recently investigated in the soleus muscle of these omega3-depleted rats. The present study deals with the triglyceride fatty acid content and pattern of the soleus muscle in control animals and omega3-depleted rats. Some of the latter rats were injected intravenously 60-120 minutes before sacrifice with either an omega3 fatty acid-rich medium-chain triglyceride/fish oil emulsion (omega3-FO rats) or a control medium-chain triglyceride/olive oil emulsion (omega3-OO rats). The total fatty acid content of triglycerides was comparable in control and omega3-depleted rats and, in both cases, inversely related to their C20:4omega6 relative content. At variance with the situation found in control rats, no long-chain polyunsaturated omega3 fatty acid (C18:3omega3, C20:5omega3, C22:5omega3, C22:6omega3) was detected in the omega3-depleted rats. Unexpectedly, the triglyceride content in most long-chain polyunsaturated omega6 fatty acids (C18:2omega6, C20:3omega6, C20:4omega6 and C22:4omega6) had also decreased in the latter rats. Moreover, the activity of Delta9-desaturase was apparently increased in the omega3-depleted rats, as judged from the C16:1omega7/C16:0 and C18:1omega9/C18:0 ratios. The omega3-FO rats differed from omega3-OO rats by a lower contribution of C18:2omega6 metabolites (C18:3omega6, C20:3omega6, C20:4omega6 and C22:4omega6). These findings indicate that the prior injection of the medium-chain triglyceride/fish oil emulsion, known to increase the muscle phospholipid content in long-chain polyunsaturated omega3 fatty acids, may nevertheless accentuate the depletion in long-chain polyunsaturated omega6 fatty acids otherwise found in the triglycerides of omega3-depleted rats. Such a dual effect is reminiscent of that observed, under the same experimental conditions, for selected variables in D-glucose metabolism in the soleus muscle.     

Changes in myocardial lipid composition during surgery with cold and chemical cardioplegia

The changes of children myocardium lipid composition were studied for the first time during surgical intervention under cold crystalloid cardioplegia. The surgical intervention was performed as a result of congenital heart disease--atrial septal defect. It was shown that the quantity of short chain fatty acids decreased and the amount of long chain fatty acids increased in the content of phospholipid fraction. Simultaneously the amount of linoleic (C18:2 omega 6), of docosahexaenoic (C22:6 omega 3) and of some other fatty acids decreased in the content of cholesterol esthers. The accumulation of free linoleic (C18:2 omega:6), (C18:2 omega:4) and linolenic (C18:3 omega:6) acids was found. Reperfusion caused the additional changes of myocardium lipid composition. The amount of palmitic (C16:0) acid decreased by 30%. The quantity of some other saturated free fatty acids also diminished. Simultaneously the content of free oleic (C18:1 omega 9) also decreased as a consequence of lipid peroxidative processes activation. The ratio of omega 6/omega 3 increased during the few first minutes of reperfusion in the fraction of free fatty acids and cholesterol esthers.     

Prenatal and postnatal transfer of fatty acids from mother to pup in the hooded seal

Unlike most mammals, hooded seal (Cystophora cristata) pups are born with a substantial layer of adipose tissue. Subsequently, during the brief lactation period of only 4 days, fasting mothers mobilize enormous amounts of lipid from blubber and secrete milk (60% fat) at rates of 10 kg·day^-1. Pups gain 7 kg·day^-1 due primarily to the deposition of fat in blubber. We measured blubber content and fatty acid composition of blubber and milk in hooded seal mother-pup pairs at birth and over the 4-day lactation period to examine the nature and source of fetal lipids, the incorporation of maternal blubber fatty acids into milk lipid, and patterns of fatty acid deposition in suckling young. The fatty acid composition of the blubber of the newborn was notably different from that of its mother. Fetal deposition was likely due to a combination of both fetal synthesis and direct placental transfer of maternal circulating fatty acids. The blubber of the newborn was characterized by high levels (>90% of total fatty acids) of saturated and monounsaturated fatty acids of primarily endogenous origin. In particular, the fetus appeared to have high Δ-9 desaturase activity as evidenced by the large amounts of 14:1n-5 (4.2%) and 16:1n-7 (37.0%) in newborn blubber compared to maternal blubber (0.2% and 14.1%, respectively). Nevertheless, essential and long-chain polyunsaturated fatty acids of the n-3 and n-6 families, which could only have originated by direct transfer from the mother, comprised>7% of pup blubber fatty acids and indicated greater rates of placental transfer than found in humans. In hooded seal mothers, rapid lipid transfer during the brief lactation period appeared to be facilitated by direct incorporation of mobilized fatty acids into milk. Although some differences in proportions of specific fatty acids were found between milk and maternal blubber, most of these differences declined over the course of lactation. However, selective mobilization of 20:5n-3 from maternal blubber into milk was apparent throughout lactation and resulted in elevated levels in pup blubber at weaning compared to maternal blubber. Ingested fatty acids were deposited directly and without modification into the blubber of pups, and by 4 days the fatty acid composition of pup blubber was virtually identical to that of the milk consumed.     

Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition

We investigated whether supplementation with arachidonic acid (20:4 omega 6; AA), or a combination of AA and docosahexaenoic acid (22:6 omega 3; DHA) would affect human milk polyunsaturated fatty acid (PUFA) composition. Ten women were daily supplemented with 300 mg AA, eight with 300 mg AA, 110 mg eicosapentaenoic acid (20:5 omega 3; EPA) and 400 mg DHA, for one week and eight women served as unsupplemented controls. Milk samples were collected on days 0, 1 and 7. The fatty acid composition of the milk was analyzed by capillary gas chromatography with flame ionisation detection. Supplementation with AA alone had no effect on breastmilk AA, but tended to reduce EPA and DHA levels. Administration of a combination of AA, EPA and DHA tended to increase both milk AA and long chain PUFA (LCPUFA)omega 3 content. A larger simultaneous increase of milk AA, DHA and EPA than observed in the present study can probably be accomplished by the use of a combination of a lower LCPUFA omega 6/LCPUFA omega 3 ratio and higher AA, EPA and DHA dosages.     

Effects of dietary omega-6 and omega-3 fatty acids on levels of long chain polyunsaturated fatty acids in erythrocytes]

C18:2 omega 6/C18:3 omega 3 ratio was lowered in the diet of Elderly subjects. This was done by the replacement of usual sunflower oil by rapeseed oil or by supplementing soybean oil. This diet modification induced an increase of EPA (C20:5 omega 3) and DHA (C22:6 omega 3) in red cell phospholipids. The omega 6 fatty acids (C18:2 and C20:4) were slightly modified. Therefore, dietary C18:2 omega 6/C18:3 omega 3 ratio, seems to play an important role in the determination of membrane highly unsaturated fatty acid levels.     

Omega 6 to omega 3 fatty acid imbalance early in life leads to persistent reductions in DHA levels in glycerophospholipids in rat hypothalamus even after long-term omega 3 fatty acid repletion

Failure to provide omega 3 fatty acids in the perinatal period results in alterations in nerve growth factor levels, dopamine production and permanent elevations in blood pressure. The present study investigated whether changes in brain (i.e., hypothalamus) glycerophospholipid fatty acid profiles induced by a diet rich in omega 6 fatty acids and very low in alpha-linolenic acid (ALA) during pregnancy and the perinatal period could be reversed by subsequent feeding of a diet containing ALA. Female rats (6 per group) were mated and fed either a low ALA diet or a control diet containing ALA throughout pregnancy and until weaning of the pups at 3 weeks. At weaning, the pups (20 per group) remained on the diet of their mothers until 9 weeks, when half the pups were switched onto the other diet, thus generating four groups of animals. At 33 weeks, pups were killed, the hypothalamus dissected from the male rats and analysed for glycerophospholipid fatty acids. In the animals fed the diet with very little ALA and then re-fed the control diet containing high levels of ALA for 24 weeks, the DHA levels were still significantly less than the control values in PE, PS and PI fractions, by 9%, 18% and 34%, respectively. In this group, but not in the other dietary groups, ALA was detected in all glycerophospholipid classes at 0.2-1.7% of the total fatty acids. The results suggest that omega 6-3 PUFA imbalance early in life leads to irreversible changes in hypothalamic composition. The increased ALA and reduced DHA proportions in the animals re-fed ALA in later life are consistent with a dysfunction or down-regulation of the conversion of ALA to 18:4n-3 by the delta-6 desaturase.     

Omega-3 fatty acids increase the arachidonic acid content of liver cholesterol ester and plasma triacylglycerol fractions in the rat.

Recent studies have demonstrated that dietary fish oils rich in eicosapentaenoic acid (C20:5,omega 3) lower the content of arachidonic acid and its metabolites in plasma and tissue phospholipids. The present study examined the fatty acid composition of cholesterol ester and triacylglycerol fractions from plasma and livers of rats fed diets enriched with saturated fatty acids (beef tallow), alpha-linolenic acid (linseed oil) or eicosapentaenoic acid (fish oil). Feeding diets containing linseed oil or fish oil for 28 days increased arachidonic acid (C20:4,omega 6) levels in the cholesterol ester fraction of liver and in the triacylglycerol fraction of the plasma lipids. Plasma cholesterol esters were depleted of C20:4,omega 6 after feeding of the diet containing either linseed oil or fish oil. The changes in C20:4,omega 6 content cannot be explained by alterations in cholesterol ester or triacylglycerol pools of plasma and liver. These results suggest that the decrease in phospholipid C20:4,omega 6 content generally observed after fish oil consumption may be partly due to a shift of C20:4,omega 6 from phospholipid to the triacylglycerol and/or cholesterol ester pools in the same tissue. Triacylglycerols and cholesterol esters may therefore play a buffering role in the homeostatic maintenance of tissue phospholipid levels of arachidonic acid.     

Metabolic interactions among polyunsaturated fatty acids in response to an atherogenic diet.

The distribution of fatty acids in hepatic lipids of dogs fed a diet containing hydrogenated coconut oil as the only source of lipid, changed in the manner characteristic of essential fatty acid deficiency. Cholesterol supplementation of this diet accentuated these changes resulting in further increases in oleic and eicosatrienoic acids and decreases in the distribution of linoleic and arachidonic acids. Two eicosatrienoic acid isomers, 20:3 omega9, derived from oleic acid and 20:3 omega6, an intermediate in the biosynthesis of arachidonic acid from linoleic acid, were identified. The increase of the 20:3 omega6 isomer was found, somewhat unexpectedly, to be greater than that of 20:3 omega9, the isomer normally associated with EFA defiency. The increase in 20:3 omega6 was probably due in part, but not completely, to competitive inhibition by the increased concentration of 20:3 omega9 on the desaturation reaction whereby 20:3 omega6 is converted to arachidonic acid.     

Accelerated clearance of plasma triglycerides and free fatty acids in omega3-depleted rats.

The present study aims mainly at exploring the effects of a severe depletion in polyunsaturated long-chain omega3 fatty acids upon the fate of circulating lipids. The plasma concentration and fatty acid pattern of triglycerides, diglycerides, free fatty acids, and phospholipids were measured in omega3-depleted and control rats injected intravenously one hour before sacrifice with either saline, a control medium-chain triglyceride:olive oil emulsion or a medium-chain triglyceride:fish oil emulsion recently found to rapidly increase the phospholipid content of C20:5omega3 and C22:6omega3 in different cell types. The estimated fractional removal rate of the injected triglycerides and the clearance of free fatty acids from circulation were both higher in omega3-depleted rats than in control animals. The injection of the lipid emulsions apparently inhibited intracellular lipolysis, this being least pronounced in omega3-depleted rats. The increased clearance of circulating triglycerides and unesterified fatty acids in omega3-depleted rats may favor the cellular accumulation of lipids. In turn, such an accumulation and the lesser regulatory inhibition of tissular lipolysis may match the increased clearance of circulating unesterified fatty acids and, hence, account for the lack of any significant difference in plasma unesterified fatty acid concentration between these and control animals.     

Impact of maternal dietary n-3 and n-6 fatty acids on milk medium-chain fatty acids and the implications for neonatal liver metabolism

Levels of n-6, n-3, and medium-chain fatty acids (MCFA) in milk are highly variable. Higher carbohydrate intakes are associated with increased mammary gland MCFA synthesis, but the role of unsaturated fatty acids for milk MCFA secretion is unclear. This study addressed whether n-6 and n-3 fatty acids, which are known to inhibit hepatic fatty acid synthesis, influence MCFA in rat and human milk and the implications of varying MCFA, n-6, and n-3 fatty acids in rat milk for metabolic regulation in the neonatal liver. Rats were fed a low-fat diet or one of six higher-fat diets, varying in 16:0, 18:1n-9, 18:2n-6, 18:3n-3, and long-chain (LC) n-3 fatty acids. Higher maternal dietary 18:2n-6 or 18:3n-3 did not influence milk MCFA, but lower maternal plasma triglycerides, due to either a low-fat or a high-fat high-LC n-3 diet led to higher milk MCFA. MCFA levels were inversely associated with 18:1n-9, 18:2n-6, and 18:3n-3 in human milk, likely reflecting the association between dietary total fat and unsaturated fatty acids. High LC n-3 fatty acid in rat milk was associated with lower hepatic Pklr, Acly, Fasn, and Scd1 and higher Hmgcs2 in the milk-fed rat neonate, with no effect of milk 18:1n-9, 18:2n-6, or MCFA. These studies show that the dietary fatty acid composition does not impact MCFA secretion in milk, but the fatty acid composition of milk, particularly the LC n-3 fatty acid, is relevant to hepatic metabolic regulation in the milk-fed neonate.     

Dietary lipid modulation of rat liver mitochondrial succinate: cytochrome c reductase

Diets supplemented with high levels of either saturated fatty acids or unsaturated fatty acids were fed to adult rats for a period of 9 weeks and changes in the liver mitochondrial membrane phospholipid fatty acid composition and thermal behaviour of succinate: cytochrome c reductase were determined. The dietary treatment induced a change in the omega 6 to omega 3 unsaturated fatty acid ratio in the membrane lipids, with the ratio being highest with the unsaturated fatty acid and lowest with the saturated fatty acid diet. Arrhenius plots of succinate: cytochrome c reductase activity exhibited differences in both critical temperature (Tf) and Arrhenius activation energy (Ea) depending on the type of dietary treatment. The Tf was elevated from 23 degrees C in control to 32 degrees C in the saturated fatty acid-supplemented group. No significant effect on the Tf was observed in the unsaturated fatty acid-supplemented group however higher Ea values were observed due to the unsaturated fatty acid diet. The changes in succinate: cytochrome c reductase are probably due to changes in the lipid-protein interactions in the membrane, induced by the dietary lipid supplementation.     

Dietary lipids and forages interactions on cow and goat milk fatty acid composition and sensory properties

This review summarises the known effects of dietary factors on bovine and caprine milk fatty acid composition, as well as the regulation of cow and goat mammary lipid secretion. Special attention is given to fatty acids that could play a role for human health, such as saturated fatty acids, oleic acid, n-6- or n-3-C18 to C22 polyunsaturated fatty acids, trans isomers of C18:1 and C18:2, and isomers of conjugated linoleic acid (CLA). The main dietary factors taken into account are the nature of forages, including pasture, the forage:concentrate ratio and diet starch content, and the supplementation of dairy rations with crude or processed vegetable oils or oilseeds, and vitamin E. A particular emphasis is given to studies on interactions between these dietary factors, which show that there is a considerable plasticity of ruminant milk fatty acid composition. Despite the existence of several studies on the effects of dietary factors on the sensorial quality of milk and dairy products, there is a need to evaluate more deeply how the different feeding strategies could change the nutritional, sensorial and technological aspects of milk fat quality.     

Regulation of PUFA metabolism: pharmacological and toxicological aspects

Levels of the long-chain polyunsaturated fatty acids (LCP) of the n-6 and n-3 series in animal plasma and cells are directly or indirectly dependent upon the intakes of either their precursors, the short-chain polyunsaturated fatty acids (SCP), linoleic (LA, 18:2 n-6) and alpha linolenic acid (ALA, 18:3 n-3), respectively, and/or of the preformed products (arachidonic, 20:4 n-6) and eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3). We report here that pharmacological agents and cytotoxic compounds significantly affect the production of LCP from SCP in cultured cells. Using labelled substrates and radio HPLC separations, we observed that the potent hypocholesterolemic agent, simvastatin, activates the formation of AA from LA, mainly acting at the delta5 desaturation step, and increases also the mRNA levels, in cultured monocytic cells (THP-1). Elevation of AA occurs also in plasma lipids of hyperlipemic patients treated with statins (but not with fibrates). Conversely, oxysterols (mainly 7-beta-oxysterol), which are detected in circulating lipoproteins of rabbits on a hypercholesterolemic diet, potently inhibit the synthesis of AA from LA in hepatocytic cell lines (Hep-G2). At the same time plasma levels o AA are reduced vs controls, in spite of an identical intake of LA. Finally, on the basis of previous work showing reduced levels of LCP, mainly DHA, in the milk of cigarette-smoking mothers, we have observed that the incubation of human mammary gland cells with sera exposed to cigarette smoke results in marked inhibition of the production of DHA from ALA. The products in smoke responsible for this effect, are being identified through mass spectrometric techniques. In conclusion, pharmacological agents and toxic compounds, such as oxysterols and smoke products affect key steps in the synthesis of the LCP, major bioregulators in mammalian cells.     

Docosahexaenoic acid transfer into human milk after dietary supplementation: a randomized clinical trial

Docosahexaenoic acid (DHA) is important for infant development. The DHA transfer from maternal diet into human milk has not been investigated in detail. We studied the effects of DHA supplementation on the fatty acid composition of human milk and the secretion of dietary (13)C-labeled fatty acids, including DHA, into human milk. Ten lactating women were randomized to consume, from 4 to 6 weeks postpartum, an oil rich in DHA (DHASCO, 200 mg of DHA/day) (n = 5) or a placebo oil (n = 5). Dietary intakes were followed by 7-day protocols. On study day 14 a single dose of [U-(13)C]DHASCO was given orally, milk samples were collected over 48 h, and milk production was recorded. Milk fatty acid composition was determined by gas-liquid chromatography and isotopic enrichment was determined by gas chromatography- combustion-isotope ratio mass spectrometry (GC-C-IRMS). Milk DHA content did not differ between the supplemented and placebo group at study entry (0.29 vs. 0.28 wt%, median). After 2 weeks of supplementation the milk DHA content was almost 2-fold higher in the supplemented versus placebo group (0.37 vs. 0.21 wt%, P = 0.003). Cumulative recovery of [(13)C]palmitic, [(13)C]oleic, and [(13)C]docosahexaenoic acids in human milk at 48 h was similar between supplemented and placebo groups (palmitic acid 7.40 vs. 8. 14%, oleic acid 9.14 vs. 9.97%, and docosahexaenoic acid 9.09 vs. 8. 03% of dose, respectively). Notable lower recovery was observed for [(13)C]myristic acid in both the supplemented and placebo groups, 0. 62 versus 0.77% of dose.Dietary DHA supplementation increases the DHA content in human milk. DHA transfer from the diet into human milk is comparable to palmitic and oleic acid transfer.     

Dietary fish oil and flaxseed for rabbit does: fatty acids distribution and Δ6-desaturase enzyme expression of different tissues

Standard feeds are imbalanced in term of n-6/n-3 polyunsaturated fatty acids (PUFA) ratio, with a low proportion of the latter. The reproductive system appears to be strongly affected by administration of n-3 PUFA, and ingredients rich in α-linolenic acid (ALA; i.e. vegetable sources) or EPA and DHA acids (i.e. fish oil) can be included in animal diets to balance PUFA intake. The aim of this study was to evaluate the effect of dietary supplementation with flaxseed (ALA) or fish oil (EPA and DHA) on PUFA metabolism in rabbit does. A total of 60 New Zealand White female rabbits were assigned to three experimental groups: control group, FLAX group fed 10% extruded flaxseed and FISH group fed 3% fish oil. Blood, milk, liver and ovaries were collected from the does to assess the lipid composition; furthermore, FADS2 gene expression was assessed in liver and ovary tissues. Reproductive performance of does was also recorded. The fertility rate and number of weaned rabbits improved with n-3 dietary supplementation: does at first parity showed the lowest reproductive results, but the administration of n-3 reduced the gap between primiparous and multiparous does. Feed consumption and milk production were not affected by the feeding regime. The fatty acid composition of milk, plasma, liver and ovaries were widely influenced by diet, showing higher concentrations of n-3 long-chain PUFA (LCP) in does fed with n-3 enriched diets. FISH diet resulted in the highest n-3 LCP enrichment, whereas in the FLAX group, this increase was lower. Blood and milk showed low levels of LCP, whereas liver and ovaries were the main sites of n-3 LCP synthesis and accumulation. Accordingly, although the liver is the main metabolic centre for LCP synthesis, ovaries also have a prominent role in LCP generation. FADS2 expression in liver and ovary tissue was downregulated by FISH administration. In conclusion, the enrichment of diets with n-3 PUFA could be an effective strategy for improving the reproductive performance of does.