Ethanol Inhalation and Dietary N-6, N-3, and N-9 Fatty Acids in the Rat: Effect on Platelet and Aortic Fatty Acid Composition

The effects of 18-carbon n-6, n-3, and n-9 fatty acid diets and ethanol exposure on the fatty acyl composition of platelets and vascular tissue were examined. An experimental design was devised to control the dietary content of 18-carbon fatty acids. The levels of 18:3n6, 18:3n3 and 18:1n9 were varied by a formulation of dietary oils which contained similar proportions of 18:2n6. Male Sprague-Dawley rats were fed a purified diet containing 11% by weight of either borage oil (BOR) rich in 18:3n6, linseed/safflower oil (LSO) rich in 18:3n3, or sesame oil (SES) rich in 18:1n9 for 7 weeks and exposed to ethanol vapors by means of inhalation for the final 6 days of the dietary regimen. Moderate blood ethanol levels of 118 +/- 6.6 mg/dl were obtained. Total lipids were extracted from platelets and aortae, and the fatty acid distributions were analyzed by gas chromatography. BOR feeding resulted in increases in the proportion of n-6 fatty acids (18:3n6, 20:3n6, 20:4n6) in platelets and aorta. Animals fed the LSO diet had increased levels of n-3 fatty acids (18:3n3, 20:5n3, 22:6n3). The SES-based diet resulted in an increase in 18:1n9 in both aorta and platelets. Following ethanol exposure alone, the most marked change in the fatty acid profile was a decrease in 20:4n6 in the platelet. This effect was not observed in rats supplemented with BOR. No significant changes were observed in the aortic fatty acid content at this level of ethanol exposure. The results suggested that, in the rat, a diet enriched with BOR effectively prevented ethanol-induced alterations in platelet fatty acid composition.     

Effect of the linolenic acid content of the mother's diet on the polyunsaturated fatty acid composition of subcellular fractions in brain development in the rat

In order to determine precisely the respective roles of linolenic acid and linoleic acid in the maternal diet on rat brain subcellular fractions during development, we used two diets with different percentages of linolenic acid (18:3 n-3). The animals were fed peanut oil (group A) or soybean oil (group B) during pregnancy and throughout lactation. Nature and amount of essential fatty acids had no incidence on saturated and monounsaturated fatty acid distributions in myelin, synaptosomal, mitochondrial and microsomal fractions. In adult rats, all subcellular fractions are marked by an increase of n-3 fatty acid and a decrease of n-6 fatty acid levels in group B compared to group A. In 15-day-old animals, on the contrary, only the synaptosomal fractions are significantly affected by the diet. Independent of diet, brain development is marked by a decrease of n-6 fatty acids in all subcellular fractions; on the other hand, the n-3 fatty acid level is increased in the synaptosomal and mitochondrial fractions, and decrease in the myelin and microsomal fractions. The sum of (n-3 + n-6) fatty acids remains constant in group B and in group A in all subcellular fractions. Finally, under our experimental conditions, we found no marked effect of diet composition upon linoleic acid conversion to arachidonic acid; only the delta 4-7-10-13-16-docosapentaenoic acid (22:5 n-6) level decreased in group B. delta 7-10-13-16-19-Docosapentaenoic acid (22:5 n-3) seemed to be a better substrate for delta 4 desaturase than delta 7-10-13-16-docosatetraenoic acid (22:4 n-6).     

Comparative effects of feeding different fats on fatty acid composition of major individual phospholipids of rat hearts

Comparative effects of feeding dietary linoleic (corn oil), oleic (olive oil), alpha-linolenic (soybean oil) and polyunsaturated fatty acids (fish oil) on lipid content and fatty acid composition of major individual phospholipids of rat hearts were examined. Feeding different diets did not result in lipid accumulation in the heart. Total triglyceride, nonesterified fatty acid, cholesteryl ester and phospholipid levels of heart tissue were not affected by the type of dietary fatty acid. However, heart free cholesterol levels decreased in both animals fed the olive and the fish oil diets. The percentage of individual phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and cardiolipin (CL) did not modify by changes in the dietary fat composition. Heart tissue from animals fed on olive oil were enriched with 18:1 (n-9 + n-7) fatty acid in all phospholipid fractions. Animals fed corn oil contained higher proportions of 18:2 (n-6) for PC, PE and CL, and the ingestion of the soybean oil diet increased 18:2 (n-6) for PC and CL in the same proportion as the ingestion of the corn oil diet. The levels of 22:6 (n-3) were increased in the fish oil-fed group, accompanied by both a decrease in total (n-6) fatty acids and an increase in total (n-3) fatty acids in the three phospholipid fractions. The 20:5 (n-3) was only detected in these animals. These results show that olive oil is as effective as fish oil in reducing heart cholesterol content and support earlier works suggesting the role of fish oil in preventing cardiovascular disease.     

Fatty acid alterations in liver peroxisomes from n-3-deficient mice

A diet deficient in n-3 fatty acids dramatically reduces docosahexaenoic acid (4.8-fold) and 20:5n-3 content in murine total peroxisomal phospholipids, and conversely increases 22:5n-6 (17.1-fold) and also, to a lesser extent, 20:4n-6. This was also found in purified phosphatidylethanolamine and phosphatidylcholine. After changing the non-deficient diet (containing alpha-linolenic acid, ALA) to a deficient one (deficient in ALA), it took a very long time for docosahexaenoic acid concentration in peroxisomes to decline (>5 months). In contrast, after changing the deficient to a non-deficient diet, time to complete recovery was more rapid (3 weeks). Changes in 20:5n-3, 22:6n-3 and 20:4n-6 were generally stabilized within 2-4 weeks. Dietary n-3 fatty acids control the fatty acid composition of peroxisomal membranes, and thus possibly affect some of their functions.     

Fatty acid composition and estimated desaturase activities are associated with obesity and lifestyle variables in men and women

It is known that the fatty acid (FA) composition in serum cholesteryl esters to a certain extent mirrors not only the FA composition of dietary fat, but also the endogenous FA synthesis, where desaturases play an important part. A surrogate measure of delta9-, delta6- and delta5-desaturase activity can be calculated as a [product:precursor] fatty acid ratio. Delta9-desaturase activity is known to be high in conditions like diabetes, atherosclerosis and obesity. The aim of the present study was to relate the proportions of individual fatty acids in serum cholesteryl esters, as well as estimated desaturase ratios to markers of obesity and lifestyle variables (smoking, physical activity and dietary fat). We also studied gender differences. These relationships were studied in a reference population consisting of men (n=554) and women (n=295) who took part in a health survey concerning coronary heart disease in Sweden. We found positive and significant correlations between markers of obesity and the proportions of 16:0, 16:1 (n-7), 18:0, 18:3 (n-6), 20:3 (n-6), 20:4 (n-6), 20:5 (n-3), delta9 and delta6 activities, and an inverse correlation to delta5 activity and 18:2 (n-6). These relationships were independent of age and physical activity and in some cases of body mass index (BMI). For each standard deviation (SD) increase of delta9 and delta6 activities, the risk of being overweight was increased by about 60%, whereas the risk was reduced to about 30% for every SD increase of delta5 activity. Women were found to have significantly higher levels of delta9 and lower levels of delta6 desaturase activities than men. In conclusion, this study shows that a changed FA profile in serum cholesteryl esters and estimated desaturase activities are associated with obesity and lifestyle factors in men and women.     

Relationship between fat cell size and number and fatty acid composition in adipose tissue from different fat depots in overweight/obese humans

OBJECTIVE: To evaluate the body fat distribution and fat cell size and number in an overweight/obese population from both genders, and to determine the possible relationship between fat cell data from three different adipose tissue localizations (subcutaneous (SA), perivisceral and omental) and adipose tissue composition and dietary fatty acid. DESIGN: The sample consisted of 84 overweight/obese patients (29 men and 55 women) who have undergone abdominal surgery. The adipocyte size and total fat cell number was studied. Fat cell data were related with anthropometric, adipose tissue and subject's habitual diet fatty acid composition. MEASUREMENTS: Fat cell size was measured according to a Sj?str?m method from the three adipose depots. Total fat cell number was also calculated. The fatty acid composition of adipose tissue was examined by gas chromatography. The subjects diet was studied by a 7 days dietary record. RESULTS: Our data showed a negative relationship between the adipocyte size and the n-6 and n-3 fatty acids content of the SA adipose tissue (r=-0.286, P=0,040; r=-0.300, P=0.030) respectively, and the n-6 in the omental depots (r=-0.407, P=0.049) in the total population. Positive associations with the total of saturated (r=0.357, P=0.045) and negative (r=-0.544, P=0.001) with the n-9 fatty acids were observed when the relationship between the adipocyte number and the fatty acid composition of the different anatomical fat regions was studied. Dietary fatty acids composition positively correlated with fat cell size for the myristic acid (14:0) in men in the visceral depot (r=0.822, P=0.023), and for the saturated fatty acids (SFAs) in women in the omental depot (r=0.486, P=0.035). CONCLUSION: In the present study, for the first time in humans we found that n-3 and n-6 fatty acids are related to a reduced adipocyte size according to the depot localization. In contrast, adipose tissue and dietary SFAs significantly correlated with an increase in fat cell size and number. No significant associations were found between n-9 acids content and adipocyte size. However, n-9 adipose tissue fatty acids content was inversely associated with fat cell number showing that this type of fatty acid could limit hyperplasia in obese populations. The differences observed in the three different regions, perivisceral, omental and SA fat, indicate that this population adipose tissue have depot-specific differences.     

Altered fatty acid composition in the plasma, platelets, and aorta of the streptozotocin-induced diabetic rat

Decreased arachidonate levels have been described in various tissues of the streptozotocin-induced diabetic rat. However, reported arachidonate changes in platelets from diabetic patients have been variable. In this communication, we describe experiments that indicate that in the short-term streptozotocin diabetic rat (2 to 3 weeks), the fatty acid composition of plasma and red blood cell lipids was altered but remained unchanged in platelet and aorta phospholipids. The altered fatty acid composition of the diabetic red blood cells and plasma cholesterol esters and phospholipids was similar to that previously found in the diabetic liver. However, in long-term diabetes (6 weeks), the phospholipid fatty acid composition of the platelet and aorta became significantly altered. Thus, in the 6-week diabetic platelet, there were increases of linoleate, dihomo-gamma-linolenate, docosapentaenoate (C22:5n-3), and docosahexaenoate, and decreases of oleate, arachidonate, and docosatetraenoate. In the aorta, there were increases of linoleate, eicosapentaenoate, and docosahexaenoate, and decreases of arachidonate, docosatetraenoate, and docosapentaenoate (C22:5n-6). Results from these experiments indicate that the fatty acid composition of plasma and red blood cell lipids was altered in short-term diabetes (2 to 3 weeks), but that of platelet and aorta phospholipids was not changed until more prolonged diabetes was present. Insulin treatment of the diabetic rat increased the levels of palmitoleate and oleate and decreased the levels of linoleate in platelet and aorta lipids from insulin-treated diabetic rats, suggesting an overcorrection of diminished delta 9 and delta 6 fatty acid desaturation as compared with the nondiabetic control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations in polyunsaturated fatty acid composition of cardiac membrane phospholipids and alpha 1 adrenoceptor mediated phosphatidylinositol turnover

STUDY OBJECTIVE - The aim of the study was to investigate the steps at which polyunsaturated fatty acids are involved in alpha 1 adrenoceptor mediated phosphatidylinositol turnover. DESIGN - Phosphatidylinositol turnover rates were investigated after preincubating neonatal rat ventricular myocytes with culture media enriched with linoleic acid (18:2n-6) or eicosapentaenoic acid (20:5n-3) to change the polyunsaturated fatty acid composition of their membrane phospholipids. EXPERIMENTAL MATERIAL - Cardiomyocytes were isolated from ventricles of 2-4 d old Wistar rats by trypsinization and were then cultured. Experiments were started 48 h after seeding, when there was a confluent monolayer of beating cardiomyocytes. MEASUREMENTS and RESULTS - In 18:2n-6 treated cells the 18:2n-6 content in the total phospholipid fraction rose from 45 to 68 nmol.mg-1 protein; in 20:5n-6 treated cells the 20:5n-3 content rose from 1.5 to 12.5 nmol.mg-1 protein, and the docosapentaenoic acid (22:5n-3) content rose from 5.1 to 14.7 nmol.mg-1 protein. The major n-3 fatty acid, 22:6n-3 (11.4 nmol.mg-1 protein), did not change after 20:5n-3 treatment. Although the phosphatidylinositol fraction showed changes paralleling those in the total phospholipids, none were significant. In this fraction the major n-3 fatty acid appeared to be 22:5n-3 (0.4 nmol.mg-1 protein). The fatty acid treated cells were prelabelled with [3H]-inositol to estimate the rate of phosphatidylinositol-4,5-bisphosphate turnover. There were no differences in the rate of [3H]-inositolphosphate formation between control, 18:2n-6 treated cells, and 20:5n-3 treated cells. Prolonged alpha 1 adrenergic stimulation of control and treated cells did not change the polyunsaturated fatty acid composition of the total phospholipid and phosphatidylinositol fractions. CONCLUSIONS - The alpha 1 adrenoceptor mediated phosphatidylinositol turnover rate is not affected by changes in polyunsaturated fatty acid composition of membrane phospholipids, neither does prolonged alpha 1 adrenergic stimulation lead to significant depletion of any specific or total polyunsaturated fatty acids in the phosphatidylinositol lipids.     

Altered levels of n-6/n-3 fatty acids in rat heart and storage fat following variable dietary intake of linoleic acid

Fat-supplemented dies enriched with linoleic acid by the addition of 12% w/w sunflower seed oil or proportionally reduced in linoleic acid by addition of 12% mutton fat were fed to rats for 18 months before the fatty acid composition of perirenal storage fat and myocardial membranes (phospholipids) was determined. Although the fatty acid composition of perirenal fat generally reflected that of the diet, there was an inverse relationship between the consumption of n-6 and the deposition of n-9 fatty acids. In addition, enhanced deposition of oleic acid (18:1, n-9) appears to be related to the dietary intake of stearic acid (18:0). In contrast, in myocardial membranes the n-3 polyunsaturated fatty acids are found to be increased when the intake of n-6 polyunsaturated fatty acids is reduced. This is particularly evident for docosahexaenoic acid (22:6, n-3) which is significantly increased in phosphatidylcholine, phosphatidylethanolamine, and diphosphatidylglycerol fractions of myocardial membranes, when the mutton fat diet was fed. After feeding the sunflower seed oil diet, the increased consumption of linoleic acid produced only small changes in the 18:2, n-6 content of cardiac phosphatidylcholine and phosphatidylethanolamine. These major classes of membrane phospholipids also showed only small increases in 20:4, n-6. In diphosphatidylglycerol, increased 18:2, n-6 also followed increased dietary intake, but this was not accompanied by increased 20:4, n-6. These changes in myocardial phospholipid fatty acid composition are similar to those observed after short-term feeding reported previously and confirm that changes in dietary n-6/n-3 fatty acid intake affect the fatty acid composition of both myocardial membranes and storage fat. These changes persist for the duration of the feeding period.     

Erythrocyte-derived measures of membrane lipid composition in healthy men: associations with arachidonic acid at low to moderate but not high insulin sensitivity

The lipid composition of erythrocyte membranes was explored as a surrogate for that of skeletal muscle in investigations into the influence of membrane fatty acid composition on insulin sensitivity. In a preliminary study (study 1), erythrocyte and monocyte/platelet membrane fatty acid percentages were compared with those of muscle membrane in 10 otherwise healthy men undergoing orthopedic surgery. In a further study (study 2), relationships between erythrocyte membrane fatty acid concentrations and insulin sensitivity, S(I), measured using the intravenous glucose tolerance test (IVGTT), were evaluated in 30 asymptomatic men. In study 1, significant positive correlations were found between muscle and erythrocyte membrane fatty acid percentages for 16:0 saturated fatty acid (r = 0.92, P <.001), and for the 18:2n-6, 20:4n-6, 20:5n-3, and 22:5n-3 polyunsaturated fatty acids (PUFAs) (r = 0.67 to 0.83, P <.05 to.01). There were fewer and weaker associations between muscle and monocyte/platelet membrane fatty acid compositions. In study 2, highly insulin-sensitive individuals (n = 8) had significantly lower erythrocyte membrane fatty acid concentrations than those with low/normal S(I). Among those with low/normal S(I) (n = 22), S(I) correlated positively with erythrocyte membrane arachidonic acid concentration (r = 0.57, P <.01) and with total PUFAs (r = 0.46, P <.05). Indices of delta 6 and delta 5 desaturase activities were significantly higher and lower, respectively, in high compared with low/normal S(I) individuals. For a range of fatty acids, erythrocyte membrane fatty acid composition shows close associations with that of muscle membranes. Measurements in erythrocyte membranes support a role for membrane arachidonic acid content in the modulation of insulin sensitivity, specifically at low/normal insulin sensitivities.     

Fatty acid profile of erythrocyte membranes as possible biomarker of longevity

Offspring of long-lived individuals are a useful model to discover biomarkers of longevity. The lipid composition of erythrocyte membranes from 41 nonagenarian offspring was compared with 30 matched controls. Genetic loci were also tested in 280 centenarians and 280 controls to verify a potential genetic predisposition in determining unique lipid profile. Gas chromatography was employed to determine fatty acid composition, and genotyping was performed using Taqman assays. Outcomes were measured for erythrocyte membrane percentage content of saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (omega-6 and omega-3), geometrical isomers of arachidonic and oleic acids, and total trans-fatty acids. Also, allele and genotyping frequencies at endothelial-nitric oxide synthase and delta-5/delta-6 and delta-9 desaturase loci were considered. Erythrocyte membranes from nonagenarian offspring had significantly higher content of C16:1 n-7, trans C18:1 n-9, and total trans-fatty acids, and reduced content of C18:2 n-6 and C20:4 n-6. No association was detected at endothelial-nitric oxide synthase and delta-5/delta-6 and delta-9 desaturase loci that could justify genetic predisposition for the increased trans C18:1 n-9, monounsaturated fatty acids and decreased omega-6 synthesis. We concluded that erythrocyte membranes derived from nonagenarian offspring have a different lipid composition (reduced lipid peroxidation and increased membrane integrity) to that of the general population.     

Long-term saturated fat supplementation in the rat causes an increase in PGI2/TXB2 ratio of platelet and vessel wall compared to n-3 and n-6 dietary fatty acids

The effect of long-term manipulation of dietary lipid intake on platelet and vessel wall lipid composition and eicosanoid synthesis was investigated. Rats were fed a standard diet (REF diet) supplemented (12% w/w) with either sheep fat (SF), sunflower seed oil (SSO) or tuna fish oil (TFO) for a period of 15 months. Significant compositional changes both in the aorta and platelets were observed following dietary lipid treatment and differences between these tissues were particularly apparent with regard to the incorporation and conversion of n-3 fatty acids. For example, platelets displayed a selective accumulation of eicosapentaenoic acid (EPA, 20:5 n-3) over docosahexaenoic acid (DHA, 22:6, n-3), but in the aorta the proportion of DHA was considerably higher than that of EPA. In both tissues, compared to REF diet, n-3 dietary fatty acids replaced the n-6 unsaturates 20:4 and 22:4, but did not affect the proportion of linoleic acid. In contrast to aorta, the unsaturation index for platelet membrane varied significantly between dietary groups. The capacity of aorta and platelets to generate PGI2-like activity and thromboxane was unaltered by the SSO diet. However, changes were seen following SF and TFO supplementation. Rats fed the SF diet displayed a greater synthetic capacity whilst in animals maintained on TFO diet the synthesis of these two eicosanoids was considerably suppressed. The SF group displayed the highest value for PGI2/TXB2 ratio whereas TFO diet fed rats showed the lowest which may partly be due to synthesis of TXA3. The reduction in eicosanoids following the tuna fish oil supplementation can be explained on the basis of concurrent compositional changes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of different dietary fatty acid sources on erythrocyte lipids and plasma and liver essential fatty acids in hamsters fed ethanol

Hamsters fed ethanol were given three different dietary sources of essential fatty acids; safflower oil, evening primrose oil (both mainly n-6 fatty acids) or linseed oil (mainly n-3 fatty acids). After 7 weeks, plasma, erythrocyte and liver lipids and fatty acids were analyzed. Plasma and liver lipids were not significantly different in the ethanol-fed hamsters compared to the controls. Erythrocyte total phospholipid was increased only in the ethanol-fed groups given n-6 but not n-3 fatty acids. Some fatty acid changes induced by ethanol were predictable, e.g. lower 20:4 n-6 in hamsters fed n-6 fatty acids, but others were not predictable, e.g. higher 22:6 n-3 in all the ethanol-fed groups. The effect of ethanol on hamster lipids and fatty acid composition appears dependent on the predominant class of dietary fatty acids.     

Placental transfer of essential fatty acids in humans: venous-arterial difference for docosahexaenoic acid in fetal umbilical erythrocytes.

Docosahexaenoic acid [22:6(n-3); 22:6(4,-7,10,13,16,19) (DHA)] is required in quantity by the developing nervous system of the fetus. This need could be met through synthesis of DHA from linolenic acid in the fetus or through placental transfer of DHA directly. To study the placental transfer of n-3 fatty acids, we obtained umbilical and maternal blood samples from 26 healthy women and infants at parturition and measured the fatty acid composition and content of both plasma and erythrocytes. A striking finding was a considerable venous-arterial difference for DHA in the umbilical erythrocytes as a proportion of total fatty acids and in absolute concentration. This difference of 2.2 micrograms per billion erythrocytes was 6 times larger than the difference in fetal plasma, when the plasma and erythrocyte concentrations were normalized to whole blood. Most other erythrocyte fatty acids showed a similar trend. In umbilical plasma, significant venous-arterial differences were found for 16:0, 16:1, 18:2, and total saturated fatty acids. There was a similar trend for most other plasma fatty acids. Compared with maternal blood, fetal plasma and erythrocytes had higher levels of 20:4 and DHA and lower levels of 18:2 and 18:3(n - 3) fatty acids as a proportion of total fatty acids. These results suggest that erythrocytes play a major role in the necessary transport of the essential fatty acid DHA into the fetus.     

Polyunsaturated Fatty Acid Plasma Content in Groups of General Population with lowvitamin B6 or low iron serum levels

Experimental and human studies describe the adverse effect of iron or vitamin B6 deficiencies on polyunsaturated fatty acid metabolism. Iron is present in end proteins of the delta6-desaturase enzyme complex, and vitamin B6 deficiency can affect the transmethylation reaction of proteins. Plasma polyunsaturated fatty acid content was estimated in apparently healthy subjects of the general population with no consumption of fish and low vitamin B6 serum levels (< 3 microg/l; n = 21) or with low iron serum levels (men: < 12 micromol/l; women: < 10 micromol/l; n = 16) and compared to a control group (n = 22) with normal vitamin B6 and iron serum levels (in reference range). The activities of the delta6-desaturase enzyme complex were calculated as product/precursor (conversion indices). In groups of subjects with low vitamin B6 and low iron levels, delta6-desaturase activity together with delta5-desaturase activity (conversion of alpha-linolenic/18:3,n-3/ into eicosapentaenoic acid/20:5,n-3/) as well as the conversion index of docosahexaenoic acid formation (22:6,n-3) from 22:5,n-3 (second delta6-desaturase activity) were significantly reduced. The inhibition effect on fatty acid synthesis was more pronounced in subjects with low iron levels than in those with low vitamin B6 levels. The conversion indices correlated significantly positively with vitamin B6 or iron levels.     

Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets

Endogenous ligands of cannabinoid receptors have been discovered recently and include some N-acylethanolamines (NAEs; e.g., N-arachidonoylethanolamine) and some 2-acylglycerols (e.g., sn-2-arachidonoylglycerol). Previously, we found these compounds to be active biologically when administered per os in large quantities to mice. In the present work, piglets were fed diets with and without 20:4n-6 and 22:6n-3 fatty acid precursors of NAEs, in levels similar to those found in porcine milk, during the first 18 days of life, and corresponding brain NAEs were assessed. In piglets fed diets containing 20:4n-6 and 22:6n-3, there were increases in several biologically active NAEs in brain homogenates-20:4n-6 NAE (4-fold), 20:5n-3 NAE (5-fold), and 22:5n-3 and 22:6n-3 NAE (9- to 10-fold). These results support a mechanism we propose for dietary long-chain polyunsaturated fatty acids influences on brain biochemistry with presumed functional sequelae. This paradigm will enable targeted investigations to determine whether and why specific populations such as infants, elderly, or persons suffering from certain clinical conditions may benefit from dietary long-chain polyunsaturated fatty acids.     

Hepatic metabolism of dietary alpha-linolenic acid in suckling rats, and its possible importance in polyunsaturated fatty acid uptake by the brain

The presence of large amounts of long chain-polyunsaturated fatty acids (PUFA) in the brain implies an exogenous intake of unsaturated fatty acids, either as essential fatty acids, or in the form of higher homologues resulting from hepatic metabolism. To determine the influence of the diet upon the potential availability of polyunsaturated fatty acids to the brain, four different diets were used with comparable amounts of 18:2 n-6, but variable amounts of 18:3 n-3 (0.2, 1, 2 and 9%). These diets were administered to female rats from the day of mating and during the periods of gestation and lactation. Fifteen days after birth suckling animals were killed and the fatty acid distribution was studied in the serum in two lipoprotein classes (VLDL-LDL and HDL). On the whole, an increase in dietary 18:3 n-3 resulted in an increase of polyunsaturated fatty acids of the n-3 series and a decrease in fatty acids of the n-6 series. The modification chiefly concerned the terminal fatty acids in each series (22:5 n-6 and 22:6 n-3). It is noteworthy that the influence of exogenous 18:3 n-3 upon the 20:4 n-6 content of lipoproteins was not significant below 2% of 18:3 n-3 intake, a level that we have previously shown to be both necessary and sufficient to satisfy the requirements of the brain for fatty acids of the n-3 series. In the liver, the intermediary metabolism ensures an important release of long-chain polyunsaturated fatty acids, which may help to satisfy the lipid requirements of the brain.     

Alcohol consumption in rhesus monkeys depletes tissues of polyunsaturated fatty acids and alters essential fatty acid metabolism

Rhesus monkeys that were maintained on an adequate diet but with low levels of essential fatty acids (1.4 en% linoleic, 18:2n-6, and 0.08 en%, linolenic acid, 18:3n-3) became depleted of 20:4n-6, and 22: 6n-3 in their livers, plasma lipoproteins, and erythrocytes during an 18-month period of alcohol exposure (2.6 g kg(-1) day(-1)). Monkeys that consumed alcohol also had higher plasma concentrations of 4-hydroxynonenal compared to controls. The metabolism of 18:2n-6 and 18:3n-3 were evaluated in both groups of animals using deuterium-labeled substrates over a 9-day period. Alcohol consumption did not appear to have an effect on the absorption of either 2H5-18:2n-6 or 2H5-18:3n-3 ethyl esters into the circulation after a single oral dose. However, there was a greater enrichment of deuterium in the biosynthesized fatty acids, 20:4n-6 and 22:6n-3, in the plasma of the monkeys exposed to alcohol compared to controls. These results suggest that chronic alcohol exposure may lead to a stimulation of the rate at which long-chain polyunsaturated fatty acids are biosynthesized to compensate for an increase in lipid peroxidation.     

Relationship of serum polyunsaturated fatty acids with cytokines in colorectal cancer

AIM: To investigate the relationship of serum levels of polyunsaturated fatty acid(PUFA) with kinds of cytokines in colorectal cancer(CRC).METHODS: Serum samples of 100 CRC patients were collected. The concentration of total n-3 PUFA which included C18:3 n-3, C20:5 n-3, C22:5 n-3, C22:6 n-3 and the total n-6 PUFA included C18:2 n-6, C18:3 n-6, C20:3 n-6, C20:4 n-6, and C22:5 n-6 were detected onGC-2010 Plus Gas Chromatograph with a Omegawax TM 250 column. Cytokines were detected by Mag Plex TM-C microspheres. P values for the trend were estimated by creating a continuous variable using the median value within quartiles.RESULTS: Interleukin-6(IL-6) showed significantly positive association with the C20:4 n-6(P for trend = 0.004). Interferon gamma(IFN-γ) showed significant positive association with the C22:5 n-3(P for trend = 0.035). IL-8 and matrix metalloproteinase-9(MMP-9) showed significant inverse association with the C22:6 n-3(P for trend = 0.049, and 0.021). MMP-2 showed significant inverse association with the C20:5 n-3(P for trend = 0.008). MMP-7 showed significantly positive association with the ratio of n-6 PUFA and n-3 PUFA(P for trend = 0.008). MMP-7 also showed significantly inverse association with the ratio of C20:4 n-6 and(n-6 PUFA + n-3 PUFA)(P for trend = 0.024). IL-10(P for trend = 0.023) and IL-6(P for trend = 0.036) showed significantly positive association with the ratio of C20:4 n-6 and C20:5 n-3.CONCLUSION: Our data suggested that serum levels of PUFA is related to the inflammation of CRC, and also play different role in regulation of immune response.     

Changes in phospholipid fatty acid composition of mouse cardiac organelles after feeding graded amounts of docosahexaenoate in presence of high levels of linoleate. Effect on cardiac ATPase activities

Mice were fed diets containing a constant supply of linoleic acid (18:2n-6, LA) as ethyl ester representing 5% by weight of the total fat (5 wt%), in combination with graded amounts of purified docosahexaenoate (22:6n-3, DHA). Cardiac sarcoplasmic reticulum (SR) and mitochondrial phospholipids (PL) from mice fed the diet without DHA contained higher levels of n-6 long chain polyunsaturated fatty acids (PUFA) (22:4n-6 and 22:5n-6) compared to total PL of liver. In the cardiac mitochondrial PL, the level of LA, DHA, the total content of PUFA and the P/S ratio were significantly higher than in SR. A small increase in dietary DHA from 0 to 0.43 wt% induced a 3.6-fold increase in PL DHA content from both cardiac organelles, with a concurrent reduction of n-6 PUFA. The changes in fatty acid PL composition were much more moderate when dietary DHA level was increased to 0.85 and 3.74 wt%. Feeding the lowest amount of DHA resulted in a 6-fold decrease in the value of n-6/n-3 PUFA ratio and a 3.5-fold decrease in the value of 20 carbon chain/22 carbon chain PUFA ratio. DHA was readily depleted from cardiac PL, and only arachidonic acid was retained in the PL from both organelles, after feeding a fat-deficient diet. Despite these drastic modifications in PL fatty acid composition, the maximum velocity (Vm) of SR Ca2+, Mg2+-ATPase was not affected, which indicates that SR cardiac membrane adapts to changes in fatty acid composition to prevent important modifications of its functional properties. However, the Vm of mitochondrial oligomycin-sensitive ATPase was slightly increased in mice fed the lowest amount of DHA. This might be due to an increase in P/S ratio and/or to a modification of cardiolipin fatty acid composition, since this PL is required for optimum function of this enzyme. It is concluded that DHA is strongly taken up by mouse cardiac PL, even in the presence of high dietary LA levels, but its acylation into PL has only little effect on the cardiac ATPase activities.