Conservation of Docosahexaenoic Acid in Rod Outer Segments of Rat Retina During n-3 and n-6 Fatty Acid Deficiency

We investigated the mechanism by which rat retina conserves docosahexaenoic acid during essential fatty acid deficiency. Weanling female albino rats were fed diets containing either 10% by weight hydrogenated coconut oil, safflower oil, or linseed oil for 15 weeks. Plasma and rod outer segment (ROS) membranes were prepared for fatty acid and phospholipid molecular species analysis. In addition, retinas were removed for morphometric analysis. We found the following: (1) Plasma phospholipids and cholesterol esters from coconut oil, safflower oil, and linseed oil diet groups were enriched in 20:3(n-9), 20:4(n-6), and 20:5(n-3), respectively. The levels of these 20-carbon fatty acids in the ROS, however, were only slightly affected by diet. (2) The fatty acids and molecular species of ROS phospholipids from the safflower oil and coconut oil groups showed a selective replacement of 22:6(n-3) with 22:5(n-6), as evidenced by a reduction of the 22:6(n-3)-22:6(n-3) molecular species and an increase in the 22:5(n-6)-22:6(n-3) species. (3) The renewal rate of ROS integral proteins, determined by autoradiography, was 10% per day for each diet group. (4) Morphometric analysis of retinas showed no differences in the outer nuclear layer area or in ROS length between the three groups. We conclude that the conservation of 22:6(n-3) in ROS is not accomplished through reductions in the rate of membrane turnover, the total amount of ROS membranes, or in the number of rod cells. The retina may conserve 22:6(n-3) through recycling within the retina or between the retina and the pigment epithelium, or through the selective uptake of 22-carbon polyunsaturated fatty acids from the circulation.     

Interactions of saturated, n-6 and n-3 polyunsaturated fatty acids to modulate arachidonic acid metabolism

Anti-thrombotic effects of omega-3 (n-3) fatty acids are believed to be due to their ability to reduce arachidonic acid levels. Therefore, weanling rats were fed n-3 acids in the form of linseed oil (18:3n-3) or fish oil (containing 20:5n-3 and 22:6n-3) in diets containing high levels of either saturated fatty acids (hydrogenated beef tallow) or high levels of linoleic acid (safflower oil) for 4 weeks. The effect of diet on the rate-limiting enzyme of arachidonic acid biosynthesis (delta 6-desaturase) and on the lipid composition of hepatic microsomal membrane was determined. Both linseed oil- or fish oil-containing diets inhibited conversion of linoleic acid to gamma-linolenic acid. Inhibition was greater with fish oil than with linseed oil, only when fed with saturated fat. delta 6-Desaturase activity was not affected when n-3 fatty acids were fed with high levels of n-6 fatty acids. Arachidonic acid content of serum lipids and hepatic microsomal phospholipids was lower when n-3 fatty acids were fed in combination with beef tallow but not when fed with safflower oil. Similarly, n-3 fatty acids (18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3) accumulated to a greater extent when n-3 fatty acids were fed with beef tallow than with safflower oil. These observations indicate that the efficacy of n-3 fatty acids in reducing arachidonic acid level is dependent on the linoleic acid to saturated fatty acid ratio of the diet consumed.     

Effect of dietary alpha-linolenate/linoleate balance on brain lipid compositions and learning ability of rats

Spontaneously hypertensive rats (SHR) and normotensive control, Wistar/Kyoto (WKY) rats through two generations were fed a semipurified diet supplemented either with safflower oil (rich in linoleate) or with perilla oil (rich in alpha-linolenate). The cerebral lipid contents and phospholipid compositions did not differ between the two dietary groups of SHR rats. There were also no differences in the unsaturated/saturated ratios of individual phospholipids or the proportions of plasma-logens. However, the proportions of (n-3) and (n-6) fatty acids were significantly different. Decreases in the proportions of docosahexaenoate [22:6 (n-3)] in phosphatidylethanolamine and phosphatidylserine in the safflower oil group were compensated for with increases in the proportions of docosatetraenoic [22:4 (n-6)] and docosapentaenoic [22:5 (n-6)] acids as compared with the perilla oil group. These differences in phospholipid acyl chains were much smaller than the difference in the proportions of linoleate and alpha-linolenate of the diets. In a brightness-discrimination learning test, the total number of responses to the positive and negative stimuli were less in the groups fed perilla oil. However, the alpha-linolenate-deficient group took longer to decrease the frequency of R- responses and therefore longer to learn the discrimination. Consequently, the correct response ratios were higher in the perilla oil groups than in the safflower oil groups. Thus, the dietary alpha-linolenate/linoleate balance influenced the (n-3)/(n-6) balance of polyenoic fatty acids differently among brain phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal Dietary Fat and Polyunsaturated Fatty Acids in the Developing Foetal Rat Brain

Abstract: Female rats were fed pursed diets containing 10% safflower oil, which is high in linoleic acid, from approximately 2 weeks prior to mating until the 14th day of gestation. They were then fed purified diets containing safflower oil, soybean oil (containing linoleic and linolenic acids), or hydrogenated coconut oil (essential fatty acid deficient). On days 16, 18, and 21 of gestation, foetuses were removed by caesarean section and the brains were subjected to fatty acid analysis. By day 16 of gestation, the ethanolamine glycerophospholipids and combined serine-inositol glycerophospholipids were rich in polyunsaturated fatty acids, particularly arachidonic acid. Between days 16 and 21 of gestation, there was a marked increase in the C₂₂-polyunsaturated acids in these glycerophospholipids, with 225n-6 deposited in foetuses from dams fed safflower or coconut oils and 22:6n-3 deposition occurring in the soybean oil group; the effects of essential fatty acid deficiency in this period were minimal. A similar pattern was evident in the choline glycerophospholipids but this fraction contained less of the polyunsaturated acids. The data are consistent with increased placental transfer of highly unsaturated fatty acids or increased foetal synthesis of these compounds during the last week of gestation, with the actual fatty acid pattern reflecting the dietary fat available to the dam.     

Isoproterenol-induced mortality and cardiac lipids of aspirin-pretreated rats with various fat intakes

The effect of altering cardiac concentrations of precursors and inhibitors of prostaglandin synthesis by varying fat intake was determined in rats injected with the cardiotoxic drug isoproterenol, following pretreatment with aspirin or potassium phosphate buffer solution. Prior to injection, four groups of rats were fed either a low-fat diet (3.7 energy percent coconut oil 3.7 energy percent safflower oil) or a high-fat diet (3.7 energy percent safflower oil-36.4 energy percent coconut oil mixture or 40.1 energy percent safflower oil.) Mortality as well as fatty acid composition of cardiac lipids changed in response to altered kinds and amounts of fats. Mortality and cardiac C20:4/C22:6 ratio were lowered by feeding 3.7 energy percent coconut oil, and increased by feeding 40.1 energy percent safflower oil. Aspirin reduced mortality in rats fed 40.1 energy percent safflower oil, but not in rats fed other diets. Results suggest that dietary manipulations which increase tissue content of polyunsaturated fatty acids of the n-6 type relative to those of the n-3 type may increase sensitivity to isoproterenol, and that effectiveness of aspirin in reducing isoproterenol-induced mortality depends upon the n-6/n-3 ratio of cardiac fatty acids.     

Transport of n-3 fatty acids from the intestine to the retina in rats.

This study was undertaken to determine the mode of transport of the essential (n-3) fatty acids docosahexaenoic acid 22:6(n-3) and linolenic acid 18:3(n-3). Male weanling Sprague-Dawley rats received a mixture of corn oil and [14C]18:3(n-3) or [14C]22:6(n-3) by gavage. At periods of 1 to 4 days after the injection, four rats per time point were killed and samples of blood were taken via heart puncture and the livers and retinas were collected. Blood lipoproteins and plasma proteins were separated by ultracentrifugation and analyzed by HPLC. Lipids were extracted and saponified and the fatty acids were converted to phenacyl esters for separation of individual fatty acids. After 1 and 2 h, radioactivity from 18:3(n-3) and 22:6(n-3) was observed primarily in the chylomicron/very low density lipoprotein fraction. By 4 h, radioactivity in the lipoprotein fraction was greatly decreased, with a small amount of radioactivity associated with albumin in the soluble protein fraction. After 24 h, the total amount of radioactivity associated with lipoprotein was further reduced, with more than half of the remaining label occurring in association with albumin and another unidentified protein. In the liver, 22:6(n-3) was concentrated in triacylglycerols (40.7%) and phospholipids (51.1%), with a maximum specific activity at 4 h. In the rod outer segments (ROS), the specific activity of [14C]22:6(n-3) increased to a maximum at 24 h and maintained a high level even at 4 days. These data suggest that after injection, 18:3(n-3) and 22:6(n-3) are esterified to triglyceride and phospholipid by the intestinal absorptive cells and transported in chylomicrons to the liver. After conversion of 18:3(n-3) to 22:6(n-3) in the liver, the retina accumulates 22:6(n-3) which may be transported from the liver via albumin and another unidentified protein, and is retained by the rod outer segments.     

The effect of diet upon the fatty acid composition of cranial and spinal nerve lipids.

The possible basal differences in lipid class and fatty acid composition between a cranial nerve (the trigeminal nerve) and two spinal nerves (the ulnar and sciatic nerves) as well as the effects of dietary lipids on the same nerves were studied. A basal (BD) and four experimental diets containing respectively hydrogenated coconut oil (HCO), grapestone oil (GSO), olive oil (OO) and linseed oil (LSO) were used. Trigeminal lipids fatty acid composition differs significantly from sciatic and ulnar ones in the percentages of 16:0, 16:1, 18:0, 18:2 n-6, 20:0, 20:1, 20:4 n-6, 24:0, 24:1 and 22:6 n-3. Also the proportions of triacylglycerols and free cholesterol strongly differ in trigeminal and spinal nerves whereas no significant difference was detected between ulnar and sciatic nerve lipids. Following the administration of the four experimental diets for 60 days, no significant change was observed in the fatty acid pattern of trigeminal lipids while the spinal ones showed a significant increase in the proportions of the fatty acids present in large quantities in the dietary oils used (i.e.: oleic acid in the OO samples). These changes are probably linked with the rapid metabolic turnover of triacylglycerols, present in larger amounts in spinal nerve lipids.     

Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat: level of n-6 fatty acids as another critical factor

Rats fed a semipurified diet supplemented with 3% (w/w) safflower oil [Saf, n-3 fatty acid deficient, high linoleic acid (18:2n-6)] through two generations exhibit decreased correct response ratios in a brightness-discrimination learning test compared with rats fed 3% perilla oil [Per, high alpha-linolenic acid (18:3n-3)]. This is associated with a decreased DHA (22:6n-3)-to-arachidonic acid (20:4n-6) ratio in brain lipids. In the first set of experiments, dietary oil was shifted from Saf to a mixture of 2.4% safflower oil plus 0.6% DHA after weaning (Saf-DHA), but all parameters measured in the learning test were essentially unchanged. Brain 22:6n-3 content of the Saf-DHA group reached that of the Per group but the levels of 20:4n-6 and docosatetraenoic acid (22:4n-6) did not decrease to those of the Per group at the start of the test. In the second set of experiments, dietary oil was shifted to a mixture of 0.6% safflower oil plus 1.2% oleic acid (OA) plus 1.2% DHA (Saf-OA-DHA group) with 18:2n-6 content comparable to that of the Per group. The Saf-OA-DHA group exhibited a learning performance similar to that of the Per group; brain 22:6n-3, 20:4n-6, and 22:4n-6 contents were also comparable to those of the Per group. These results indicate that the altered learning behavior associated with a long-term n-3 fatty acid deficiency is reversed by supplementing 22:6n-3 after weaning, when the levels of competing n-6 fatty acids in the diet and brain lipids are limited.     

Rapid modulation of the n-3 docosahexaenoic acid levels in the brain and retina of the newly hatched chick

The newly hatched chick obtains its fatty acids almost completely from the lipids of the egg yolk as these are transferred to the developing embryo during its 21-day period of incubation. Since the diet of the laying hen greatly influences the fatty acid composition of the egg lipids, and presumably also the fatty acid composition of the resulting chick, we tested how quickly and to what extent varying the amount of n-3 fatty acids in the diet of the hen would modulate the level of n-3 fatty acids in the brain and retina of the newly hatched chick. White Leghorn hens were fed commercial or semi-purified diets supplemented with 10% fish oil, linseed oil, soy oil, or safflower oil. Eggs, together with the brain, retina, and serum of newly hatched chicks, were then analyzed for fatty acid composition. The fatty acids of egg yolk responded quickly to the hen's diet with most of the change occurring by 4 weeks. There was a linear relationship between the linolenic acid content of the diets and levels of this fatty acid in egg yolk and chick serum. In chicks from hens fed the fish oil diet, the total n-3 fatty acids, including 22:6(n-3), were elevated twofold in the brain and retina and sevenfold in serum relative to commercial diet controls. The safflower oil diet led to a very low n-3 fatty acid content in egg yolks and only 25% of the control n-3 fatty acid content in the brain and retina of chicks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of dietary alpha- and gamma-linolenic acid on tissue fatty acids in guinea pigs

Guinea pigs were fed regular chow diets supplemented with 5% (by weight) safflower oil, evening primrose oil, or linseed oil for 6 weeks. The unsaturated fatty acid content of these oils was 78.9% of 18:2n6, 74.1% of 18:2n6, and 9.2% of 18:3n6, or 21.5% of 18:2n6 and 46.9% of 18:3n3, respectively. In comparison with 18:2n6, dietary supplementation with 18:3n6 significantly increased the tissue levels of 18:3n6 and 20:3n6, whereas dietary 18:3n3 significantly elevated the levels of 18:3n3 in plasma and liver lipids. Dietary 18:3n3 also significantly increased 22:5n3 and 22:6n3 in total phospholipids. The tissue levels of 20:4n6, on the other hand, were not affected by either treatment. These data suggest that both delta 6- and delta 5 desaturation of n-6 fatty acids in guinea pigs are low, and that the metabolism of n-3 and n-6 fatty acids may be regulated by two different enzyme systems.     

Selective incorporation of n-3 and n-6 fatty acids in essential fatty acid deficient rats in response to short-term oil feeding

Essential fatty acid deficient male Sprague Dawley rats were fed for 7 days a fat-free semi-synthetic diet supplemented with 10% by weight of different oil supplements. The oil supplement was a mixture of olive, safflower and linseed oils prepared at different proportions so the dietary n-9/n-6/n-3 ratios were approximate 2/1/1, 1/2/1, 1/1/2, and 1/1/1. The fatty acid compositions of plasma and liver lipids were then examined. Our results show polyunsaturated n-6 and n-3 fatty acids were selectively incorporated into plasma and liver phospholipids, and also into plasma cholesteryl esters. A preferential incorporation of n-6 over n-3 fatty acids into plasma cholesteryl esters and phospholipids was also observed.     

Effect of dietary alpha-linolenic acid on the activity and gene expression of hepatic fatty acid oxidation enzymes

The activities of hepatic fatty acid oxidation enzymes in rats fed linseed and perilla oils rich in alpha-linolenic acid (alpha-18:3) were compared with those in the animals fed safflower oil rich in linoleic acid (18:2) and saturated fats (coconut or palm oil). Mitochondrial and peroxisomal palmitoyl-CoA (16:0-CoA) oxidation rates in the liver homogenates were significantly higher in rats fed linseed and perilla oils than in those fed saturated fats and safflower oil. The fatty oxidation rates increased as dietary levels of alpha-18:3 increased. Dietary alpha-18:3 also increased the activity of fatty acid oxidation enzymes except for 3-hydroxyacyl-CoA dehydrogenase. Unexpectedly, dietary alpha-18:3 caused great reduction in the activity of 3-hydroxyacyl-CoA dehydrogenase measured with short- and medium-chain substrates but not with long-chain substrate. Dietary alpha-18:3 significantly increased the mRNA levels of hepatic fatty acid oxidation enzymes including carnitine palmitoyltransferase I and II, mitochondrial trifunctional protein, acyl-CoA oxidase, peroxisomal bifunctional protein, mitochondrial and peroxisomal 3-ketoacyl-CoA thiolases, 2, 4-dienoyl-CoA reductase and delta3, delta2-enoyl-CoA isomerase. Fish oil rich in very long-chain n-3 fatty acids caused similar changes in hepatic fatty acid oxidation. Regarding the substrate specificity of beta-oxidation pathway, mitochondrial and peroxisomal beta-oxidation rate of alpha-18:3-CoA, relative to 16:0- and 18:2-CoAs, was higher irrespective of the substrate/albumin ratios in the assay mixture or dietary fat sources. The substrate specificity of carnitine palmitoyltransferase I appeared to be responsible for the differential mitochondrial oxidation rates of these acyl-CoA substrates. Dietary fats rich in alpha-18:3-CoA relative to safflower oil did not affect the hepatic activity of fatty acid synthase and glucose 6-phosphate dehydrogenase. It was suggested that both substrate specificities and alterations in the activities of the enzymes in beta-oxidation pathway play a significant role in the regulation of the serum lipid concentrations in rats fed alpha-18:3.     

Onset of changes in phospholipid fatty acid composition and prostaglandin synthesis following dietary manipulation with n-6 and n-3 fatty acids in the rat

A synthetic diet preparation supplemented with 10% by weight of either safflower oil, hydrogenated coconut oil containing 3% safflower oil, or 'max EPA' fish oil was fed to rats over a 8-week period. Serial measurements of serum fatty acids, serum thromboxane B2 and urinary prostaglandin excretion were taken during the treatment period to assess the rate of change in fatty acid composition and prostaglandin synthesis following dietary manipulation. There was no significant change in weight gain between the dietary groups during the treatment period. Significant changes in serum fatty acids occurred within 48 h of treatment, with the 'max EPA' oil group having arachidonic acid levels reduced by 23% (P less than 0.01) compared to the coconut oil group. Conversely, rats fed safflower oil had an 18% enhancement of arachidonic acid during the same time period. Whole blood synthesis of thromboxane B2 was significantly depressed (P less than 0.01) after 48 h in rats fed 'max EPA' oil compared to the safflower oil or coconut oil groups. This suppression reached a maximum of 65% (P less than 0.001) after 7 days of dietary 'max EPA' oil treatment. The safflower oil and coconut oil-fed groups showed the same levels of serum thromboxane B2 production over the treatment period. Urinary excretion of both 6-ketoprostaglandin F1 alpha and prostaglandin E2 varied significantly (P less than 0.01) between the groups after 7 days of dietary treatment. Rats fed 'max EPA' oil had depressed urinary prostanoid excretion compared to the safflower and coconut oil groups which remained very similar to each other. After the 8-week treatment period rats were killed and the phospholipid fatty acid composition and prostaglandin-generating capacity of platelets, aorta and renal tissue was examined. Prostanoid production by kidney cortex and medulla and segments of aorta was consistently suppressed in rats fed 'max EPA' oil. These observations correlated well with changes in the phospholipid fatty acid profiles in these tissues. This study shows rapid changes in serum fatty acids and thromboxane B2 generation following dietary manipulation, while changes in urinary excretion or prostanoid metabolites occur only after a longer time period.     

Fatty acid utilisation and metabolism in caecal enterocytes of rainbow trout (Oncorhynchus mykiss) fed dietary fish or copepod oil

A combined fatty acid metabolism assay was employed to determine fatty acid uptake and relative utilisation in enterocytes isolated from the pyloric caeca of rainbow trout. In addition, the effect of a diet high in long-chain monoenoic fatty alcohols present as wax esters in oil derived from Calanus finmarchicus, compared to a standard fish oil diet, on caecal enterocyte fatty acid metabolism was investigated. The diets were fed for 8 weeks before caecal enterocytes from each dietary group were isolated and incubated with [1-14C]fatty acids: 16:0, 18:1n-9, 18:2n-6, 18:3n-3, 20:1n-9, 20:4n-6, 20:5n-3, and 22:6n-3. Uptake was measured over 2 h with relative utilisation of different [1-14C]fatty acids calculated as a percentage of uptake. Differences in uptake were observed, with 18:1n-9 and 18:2n-6 showing the highest rates. Esterification into cellular lipids was highest with 16:0 and C18 fatty acids, accounting for over one-third of total uptake, through predominant incorporation in triacylglycerol (TAG). The overall utilisation of fatty acids in phospholipid synthesis was low, but highest with 16:0, the most prevalent fatty acid recovered in intracellular phosphatidylcholine (PC) and phosphatidylinositol (PI), although exported PC exhibited higher proportions of C20/C22 polyunsaturated fatty acids (PUFA). Other than 16:0, incorporation into PC and PI was highest with C20/C22 PUFA and 20:4n-6 respectively. Recovery of labelled 18:1n-9 in exported TAG was 3-fold greater than any other fatty acid which could be due to multiple esterification on the glycerol 'backbone' and/or increased export. Approximately 20-40% of fatty acids taken up were beta-oxidised, and was highest with 20:4n-6. Oxidation of 20:5n-3 and 22:6n-3 was also surprisingly high, although 22:6n-3 oxidation was mainly attributed to retroconversion to 20:5n-3. Metabolic modification of fatty acids by elongation-desaturation was generally low at <10% of [1-14C]fatty acid uptake. Dietary copepod oil had generally little effect on fatty acid metabolism in enterocytes, although it stimulated the elongation and desaturation of 16:0 and elongation of 18:1n-9, with radioactivity recovered in longer n-9 monoenes. The monoenoic fatty acid, 20:1n-9, abundant in copepod oil as the homologous alcohol, was poorly utilised with 80% of uptake remaining unesterified in the enterocyte. However, the fatty acid composition of pyloric caeca was not influenced by dietary copepod oil.     

The Fat-1 Mouse has Brain Docosahexaenoic Acid Levels Achievable Through Fish Oil Feeding

Fat-1 transgenic mice endogenously convert n-6 to n-3 polyunsaturated fatty acids (PUFA). The aims of this study were to test whether a) fish oil feeding can attain similar brain n-3 PUFA levels as the fat-1 mouse, and b) fat-1 mouse brain docosahexaenoic acid (22:6n-3; DHA) levels can be potentiated by fish oil feeding. Fat-1 mice and their wildtype littermates consumed either a 10% safflower oil (SO) or a 2% fish oil and 8% safflower oil chow (FO). Brain total lipid and phospholipid fraction fatty acids were analyzed using GC-FID. Wildtype mice fed FO chow had similar brain levels of DHA as fat-1 mice fed SO chow. Fat-1 mice fed FO chow had similar brain n-3 PUFA levels as fat-1 mice fed SO chow. In conclusion, brain levels of DHA in the fat-1 mouse can be obtained by and were not further augmented with fish oil feeding.     

Spray-dried milk supplemented with alpha-linolenic acid or eicosapentaenoic acid and docosahexaenoic acid decreases HMG Co A reductase activity and increases biliary secretion of lipids in rats

In our earlier study, we have shown that rats fed spray-dried milk containing alpha-linolenic acid (LNA 18:3 n-3) or eicosapentaenoic acid (EPA 20:5 n-3) and docosahexaenoic acid (DHA 22:6 n-3) had significantly lower amounts of serum and liver cholesterol. To evaluate the mechanism for hypocholesterolemic effect of n-3 fatty acids containing milk formulation, we fed male Wistar rats with spray-dried milk containing linseed oil (LSO) (source of LNA) or fish oil (FO) (source of EPA+DHA) for 8 weeks. Feeding n-3 fatty acid containing milk formulation lowered the hepatic 3-hydroxy-methylglutaryl coenzyme A (HMG Co A) activity by 17-22% compared to rats given control diet devoid of n-3 fatty acids. The cholesterol level in liver microsomes was found to be decreased by 16% and 20%, respectively, in LSO and FO containing formulation fed rats. The bile flow was enhanced to an extent of 19-23% in experimental groups compared to control animals. The biliary cholesterol and phospholipid secretion was increased to an extent of 49-55% and 140-146%, respectively, in rats fed n-3 fatty acid containing formulation. The increase in the total bile acids secretion in bile was mainly reflected on an increase in the levels of taurine conjugated bile acids. These results indicated that n-3 fatty acid containing spray-dried milk formulation would bring about the hypocholesterolemic effect by lowering HMG Co A reductase activity in liver and by increasing the secretion of bile constituents.     

Effect of different contents of extruded linseed in the sow diet on piglet fatty acid composition and hepatic desaturase expression during the post-natal period

n-3 polyunsaturated fatty acids (n-3 PUFA) contribute to the normal growth and development of numerous organs in the piglet. The fatty acid composition of piglet tissues is linked to the fatty acid composition of sow milk and, consequently, to the composition of sow diet during the gestation and lactation period. In this study, we investigated the impact of different contents of extruded linseed in the sow diet on the fatty acid composition and desaturase gene expression of piglets. Sows received a diet containing either sunflower oil (low 18:3n-3 with 18:3n-3 representing 3% of total fatty acids) or a mixture of extruded linseed and sunflower oil (medium 18:3n-3 with 9% of 18:3n-3) or extruded linseed (high 18:3n-3 with 27% of 18:3n-3) during gestation and lactation. Fatty acid composition was evaluated on sow milk and on different piglet tissues at days 0, 7, 14, 21 and 28. The postnatal evolution of delta5 (D5D) and delta6 (D6D) desaturase mRNA expression was also measured in the liver of low 18:3n-3 and high 18:3n-3 piglets. The milk of high 18:3n-3 sows had higher proportions of n-3PUFA than that of low 18:3n-3 and medium 18:3n-3 sows. Piglets suckling the high 18:3n-3 sows had greater proportions of 18:3n-3, 20:5n-3, 22:5n-3 and 22:6n-3 in the liver, and of 22:5n-3 and 22:6n-3 in the brain than low 18:3n-3 and medium 18:3n-3 piglets. D5D and D6D mRNA expressions in piglet liver were not affected by the maternal diet at any age. In conclusion, extruded linseed in the sow diet modifies the n-3PUFA status of piglets during the postnatal period. However, a minimal content of 18:3n-3 in the sow diet is necessary to increase the n-3PUFA level in piglet liver and brain. Moreover, modifications in the n-3PUFA fatty acid composition of piglet tissue seem linked to the availability of 18:3n-3 in maternal milk and not to desaturase enzyme expression.     

Intestinal responsiveness to experimental colitis in young rats is altered by maternal diet

Increasing evidence suggests that fetal and neonatal nutrition impacts later health. Aims of the present study were to determine the effect of maternal dietary fat composition on intestinal phospholipid fatty acids and responsiveness to experimental colitis in suckling rat pups. Female rats were fed isocaloric diets varying only in fat composition throughout gestation and lactation. The oils used were high (8%) in n-3 [canola oil (18:3n-3)], n-6 (72%) [safflower oil (18:2n-6)], or n-9 (78%) [high oleic acid safflower oil (18:1n-9)] fatty acids, n = 6/group. Colitis was induced on postnatal day 15 by intrarectal 2,4-dinitrobenzene sulfonic acid (DNBS) administration with vehicle (50% ethanol) and procedure (0.9% saline) controls. Jejunal and colonic phospholipids and milk fatty acids were determined. The distal colon was assessed for macroscopic damage, histology, and MPO activity. The 18:2n-6 maternal diet increased n-6 fatty acids, whereas the 18:3n-3 diet increased n-3 fatty acids in milk and pup jejunal and colonic phospholipids. Maternal diet, milk, and pup intestinal n-6-to-n-3 fatty acid ratios increased significantly in order: high 18:3n-3 < high 18:1n-9 < high 18:2n-6. DNBS administration in pups in the high 18:2n-6 group led to severe colitis with higher colonic damage scores and MPO activity than in the 18:1n-9 and 18:3n-3 groups. High maternal dietary 18:3n-3 intake was associated with colonic damage scores and MPO activity, which were not significantly different from ethanol controls. We demonstrate that maternal dietary fat influences the composition of intestinal lipids and responsiveness to experimental colitis in nursing offspring.     

Fatty acid changes in liver choline and ethanolamine glycerophospholipids in aspirin-treated rats fed linoleate, gamma-linolenate and fish oil

The effects of dietary linoleic acid, gamma-linolenic acid and marine fatty acids on the development of aspirin-induced gastric hemorrhage and the distribution of liver glycerophospholipid fatty acids in fat-deficient growing rats were studied. Aspirin (100 mg/day)-treated and nontreated rats were fed for 7 days, a mixed diet of 2.5% safflower oil and 7.5% hydrogenated coconut oil (SFO/HCO) or 7.5% fish oil (SFO/FO), or 2.5% gamma-linolenate concentrate and 7.5% fish oil (GLA/FO). Gastric hemorrhage was induced in animals by aspirin treatment to various extents. It was not affected by FO feeding, but was significantly alleviated by GLA feeding. Aspirin treatment reduced the proportions of 20:4n-6 in liver phosphatidylcholine. FO feeding (in SFO/FO and GLA/FO rats) further reduced the 20:4n-6 level and replaced it by n-3 fatty acids. GLA feeding, on the other hand, elevated the proportion of 20:4n-6. As a result, the reduction of 20:4n-6 by fish oil feeding, was less significant in GLA/FO rats than in SFO/FO rats. The degree of gastric hemorrhage appeared to relate negatively to the levels of 20:4n-6 in liver phosphatidylcholine, and to the sum of 20:4n-6 and 20:5n-3 when FO was included in the diet. It is suggested that long-chain polyunsaturated fatty acids (20:4n-6 and 20:5n-3) per se in addition to being precursors of prostaglandins, may also affect the development of gastric hemorrhage, possibly by modulating the permeability of cell membranes in the gastric mucosa.     

Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys

Rhesus monkeys given pre- and postnatal diets deficient in n-3 essential fatty acids develop low levels of docosahexaenoic acid (22:6 n-3, DHA) in the cerebral cortex and retina and impaired visual function. This highly polyunsaturated fatty acid is an important component of retinal photoreceptors and brain synaptic membranes. To study the turnover of polyunsaturated fatty acids in the brain and the reversibility of n-3 fatty acid deficiency, we fed five deficient juvenile rhesus monkeys a fish oil diet rich in DHA and other n-3 fatty acids for up to 129 weeks. The results of serial biopsy samples of the cerebral cortex indicated that the changes of brain fatty acid composition began as early as 1 week after fish oil feeding and stabilized at 12 weeks. The DHA content of the phosphatidylethanolamine of the frontal cortex increased progressively from 3.9 +/- 1.2 to 28.4 +/- 1.7 percent of total fatty acids. The n-6 fatty acid, 22:5, abnormally high in the cerebral cortex of n-3 deficient monkeys, decreased reciprocally from 16.2 +/- 3.1 to 1.6 +/- 0.4%. The half-life (t 1/2) of DHA in brain phosphatidylethanolamine was estimated to be 21 days. The fatty acids of other phospholipids in the brain (phosphatidylcholine, -serine, and -inositol) showed similar changes. The DHA content of plasma and erythrocyte phospholipids also increased greatly, with estimated half-lives of 29 and 21 days, respectively. We conclude that monkey cerebral cortex with an abnormal fatty acid composition produced by dietary n-3 fatty acid deficiency has a remarkable capacity to change its fatty acid content after dietary fish oil, both to increase 22:6 n-3 and to decrease 22:5 n-6 fatty acids. The biochemical evidence of n-3 fatty acid deficiency was completely corrected. These data imply a greater lability of the fatty acids of the phospholipids of the cerebral cortex than has been hitherto appreciated.