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.     

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.     

Retinal function in rats and guinea-pigs reared on diets low in essential fatty acids and supplemented with linoleic or linolenic acids

Rats were reared into a third generation on diets deficient in essential fatty acids supplemented with linoleic acid (18:2 n-6) or linolenic acid (18:3 n-3) with the object of depleting the retina of n-6 or n-3 fatty acids. In the rats fed 18:2 n-6 the percentage by weight of 22:6 n-3 in retinal fatty acids fell from 22.5 to 8.5% in first-generation animals but then remained unchanged in second and third generations. There was no difference in b-wave amplitudes of the electroretinogram between the rats fed 18:2 n-6 and those fed 18:3 n-3. In guinea-pigs fed purified diets low in 18:3 n-3 the percentage by weight of 22:6 n-3 in retinas fell from 8 to less than 0.5% by the third generation. However, there were no statistical differences in the b-wave amplitudes between these animals and those reared on a commercial diet. It is concluded that if n-3 fatty acids are involved in retinal function their role is too subtle to be detected by standard electroretinographic techniques.     

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.     

Essential fatty acid deficiency delays the onset of puberty in the female rat

This study assessed the effect of a dietary deficiency in the essential fatty acids (EFA) linoleic and linolenic acids on the onset of female puberty. EFA deficiency was produced in female rats by means of a semipurified diet and was biochemically documented by analyzing serum and erythrocyte fatty acid levels of more than 30 fatty acids, including all members of the n-6 and n-3 series. Levels of linoleic acid (18:2 n-6) and all n-6 derivatives, particularly arachidonic acid, were strikingly reduced. A less pronounced but clear-cut decrease in n-3 fatty acids, including docosahexaenoic acid (22:6 n-3) was also found. The times of puberty and first ovulation, as assessed by the ages at vaginal opening and first diestrus, were significantly delayed in EFA-deficient rats. The mechanisms underlying this delay appear to reside at both hypothalamic and ovarian sites. Simulation of preovulatory plasma estradiol (E2) levels via implantation of E2-containing Silastic capsules evoked a LH surge 30 h later in control juvenile rats, but not in EFA-deficient animals, indicating a delay in the development of the hypothalamic component of E2-positive feedback in the latter group. This delay appears to be due at least in part to reduced prostaglandin E2 (PGE2) synthesis, as the ability of the neurotransmitter norepinephrine to induce PGE2 release from median eminence nerve terminals was markedly reduced in EFA-deficient rats compared with that in controls. The decrease in hypothalamic PGE2 release was related to the EFA deficiency and not to reduced PG synthase activity, as determined by HPLC analysis of PG synthase products derived from exogenous [14C]arachidonic acid. Basal and hCG-stimulated PGE2 synthesis was also compromised in ovaries from EFA-deficient rats. Depressed gonadal function resulting from the EFA deficiency was further evidenced by a reduced gonadotropin receptor content, a blunted E2 response to hCG in vitro, and an increase in mean serum FSH levels. These results suggest that the delay in puberty resulting from EFA deficiency is due to a reduced availability of arachidonic acid for synthesis of bioactive metabolites. This results in delayed development of both the hypothalamic and ovarian components of the reproductive axis.     

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.     

Modification of the n-6/n-3 fatty acid ratio in the phospholipids of rat ventricular myocytes in culture by the use of synthetic media: functional and biochemical consequences in normoxic and hypoxic conditions

The respective roles of exogenous polyunsaturated fatty acids on the lipid composition, physiological properties and enzyme release was investigated on isolated cardiac muscle cells in normoxia and hypoxia. Rat neonatal ventricular myocytes were grown for 5 days in conventional serum-supplemented medium. Cells were then incubated for 24 h in fully chemically-defined media featuring a balanced fatty acid composition containing either linoleic acid (18:2 n-6) or linolenic acid (18:3 n-3) as sole polyunsaturated fatty acid source. Transmembrane potentials were monitored with microelectrodes and contractions with a photoelectric device. The radio of n-6 to n-3 phospholipid fatty acids increased from 6.3 in control cells to 20.2 in cells exposed to n-6 fatty acids (SM6) and decreased to 1.4 in those exposed to n-3 fatty acids (SM3). These modifications had no influence on the electrical and mechanical activities and on automaticity in normoxic conditions. The action potential depression under hypoxia was less severe in SM6 cells, whereas there was a better electrophysiological recovery upon reoxygenation in SM3 cells. However, the loss of lactate dehydrogenase during sustained hypoxic treatment was not affected by changes in phospholipid fatty acid pattern. These results suggest that the effect of the polyunsaturated fatty acid balance depends on the cellular function under study and on the environmental conditions.     

Effects of introducing linseed in livestock diet on blood fatty acid composition of consumers of animal products

Reducing the ratio between essential fatty acids: C18:2 n-6/C18:3 n-3 down to 5 is recommended by Nutritional Guidelines. We studied the fatty acid (FA) changes in consumers' plasma following changes in livestock diet. First, a zootechnical study introduced 5% of extruded linseed into the diet of livestock to replace other oleaginous ingredients, and on an iso-nutritional values basis. The products from linseed-fed animals contained more n-3 fatty acids (precursor alpha-linolenic and derivatives obtained by elongations and desaturations) than control animal products (issued from animals fed without linseed), and more conjugated linoleic acids (CLA). The n-6/n-3 ratio was reduced by 54% in butter, 60% in meat and 86% in eggs. Following this, a double-blind, randomised, cross-over clinical study involving 75 healthy volunteers compared plasma and erythrocyte FA profiles in consumers of animal products (from livestock fed the linseed diet or from livestock fed standard diet). It showed modifications in the FA composition of the experimental human regimen with more C18:3 n-3 (1.65 vs. 0.75 g/day), and more n-3 derivatives. The C18:2 n-6/C18:3 n-3 ratio decreased (7 vs. 15). In volunteers' plasma, C18:3 n-3 increased in the essay group (0.93 vs. 0.44% of the FA), so did n-3 derivatives and CLA. The n-6/n-3 ratio decreased from 14.3 to 10.2. In erythrocytes, C20:5 n-3 increased in the essay group (0.59 vs. 0.45%) and so did C22:6 n-3. The n-6/n-3 ratio decreased in parallel from 4.2 to 3.8. Without any changes in consumers' eating habits, foodstuffs from animals fed linseed diets induced significant modifications of human plasma and erythrocyte fatty acid composition (comparable to that noted under the 'Cretan' diet) and a sharp increase in CLA.     

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.     

Effects of dietary alpha- and gamma-linolenic acid on lipid metabolism in young and adult rats

The effect of age on lipid metabolism was studied in rats fed diets containing safflower oil (SFO, 78% linoleic acid), evening primrose oil (EPO, 9.4% gamma-linolenic acid and 70% linoleic acid) or the mixture of safflower and linseed oil (SLO, 10.2% alpha-linolenic acid and 68% linoleic acid). The activity of hepatic HMG-CoA reductase declined with age in all groups. In adult rats, the reductase activity was high in the EPO group and low in the SLO group. The activity of hepatic cholesterol 7 alpha-hydroxylase was independent of the diet or age. Hepatic delta 6-desaturase activity was low in adult rats fed EPO. In liver microsomal phospholipids, the percentage of 22:5 n-6 decreased while that of 22:6 n-3 increased with age. The ratio of linoleate metabolites to linoleate was high in the EPO group and low in the SLO group. Liver and serum cholesterol increased with age only in rats fed the SLO diet. Thus, the results indicated an enhanced susceptibility to dietary fats with age.     

The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids

Rats were fed either a high linolenic acid (perilla oil) or high eicosapentaenoic + docosahexaenoic acid (fish oil) diet (8%), and the fatty acid and molecular species composition of ethanolamine phosphoglycerides was determined. Gene expression pattern resulting from the feeding of n-3 fatty acids also was studied. Perilla oil feeding, in contrast to fish oil feeding, was not reflected in total fatty acid composition of ethanolamine phosphoglycerides. Levels of the alkenylacyl subclass of ethanolamine phosphoglycerides increased in response to feeding. Similarly, levels of diacyl phosphatidylethanolamine molecular species containing docosahexaenoic acid (18:0/22:6) were higher in perilla-fed or fish oil-fed rat brains whereas those in ethanolamine plasmalogens remained unchanged. Because plasmalogen levels in the brains of rats fed a n-3 fatty acid-enriched diet increased, it is plausible, however, that docosahexaenoic acid taken up from the food or formed from linolenic acid was deposited in this phospholipid subclass. Using cDNA microarrays, 55 genes were found to be overexpressed and 47 were suppressed relative to controls by both dietary regimens. The altered genes included those controlling synaptic plasticity, cytosceleton and membrane association, signal transduction, ion channel formation, energy metabolism, and regulatory proteins. This effect seems to be independent of the chain length of fatty acids, but the n-3 structure appears to be important. Because n-3 polyunsaturated fatty acids have been shown to play an important role in maintaining normal mental functions and docosahexaenoic acid-containing ethanolamine phosphoglyceride (18:0/22:6) molecular species accumulated in response to n-3 fatty acid feeding, a casual relationship between the two events can be surmised.     

Fatty acid compositions of serum lipids, erythrocytes, and platelets in insulin-dependent diabetic women

The fatty acid composition of serum lipids, erythrocytes, platelets, and diet was studied in women with insulin-dependent diabetes (IDDM) and in normal subjects matched for age, sex, body weight, and serum lipid levels. The dietary intake of linoleic acid was higher in IDDM patients than in the normal subjects. The linoleic acid content of serum triglycerides, cholesterol esters, and phospholipids and of red cells and platelets were elevated in patients with IDDM proportionately to their dietary linoleate intake. The linoleic acid content of serum lipids, but not of diet, was significantly correlated with glycosylated hemoglobin A1c in IDDM patients. However, the serum lipid content of arachidonic acid and other n-6 polyunsaturated fatty acids, which are metabolites of linoleic acid, was decreased in IDDM patients, but these metabolites were normal or increased in their cell membranes. The contents of n-3 polyunsaturated fatty acids were decreased in serum and platelet lipids and tended to be increased in erythrocyte membranes of diabetic patients. The results suggest that elongation and desaturation of essential fatty acids, linoleic acid in particular, are decreased in women with IDDM.     

Effects of Prenatal Ethanol and Long-Chain n-3 Fatty Acid Supplementation on Development in Mice. 2. Fatty Acid Composition of Brain Membrane Phospholipids

Pregnant mice were fed equivalent daily amounts of a liquid diet containing 25% (kcal) ethanol, or with maltose dextrin substituted isocalorically for ethanol. The diet also contained 20% oil; this was either of two mixtures, one comprised of predominantly n-6 (18:2n-6) fatty acids, and the other containing an equivalent amount of n-6, but supplemented with a source of long chain n-3 (20:5n-3, 22:6n-3) fatty acids. An additional control group was fed lab chow ad libitum. The treatment was implemented from day 7 to 17 of gestation, whereafter all groups were fed lab chow. Birth occurred on day 19, and the fatty acid composition of the brain membrane phospholipids was determined in the pups 3 days after birth (day 22 postconception) and again, 10 days later (day 32 postconception). On day 22 the polyunsaturated fatty acid (PUFA) composition of the brain phospholipids reflected dietary availability, with the n-3/n-6 ratio higher in the n-3 groups; this was decreased by ethanol in the phosphatidylcholine (PC) fraction. The dietary effect was still apparent on day 32; again ethanol reduced this in both the PC and phosphatidylethanolamine (PE) fractions. The n-3 oil, but not ethanol, increased the 20:3n-6/20:4n-6 ratio, indicative of an inhibition of the activity of delta-5 desaturase. With respect to the 22:C compounds, the n-3 oil decreased the levels of 22:5n-6, while increasing those of 22:6n-3, but generally the sum of these two fatty acids remained unchanged. Ethanol decreased levels of 22:5n-6, and, on day 32, also decreased those of 22:6n-3, resulting in a decrease in the sum of these 22:C PUFA.     

Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants.

It is becoming clear that an adequate level of long-chain highly unsaturated fatty acids in the nervous system is required for optimal function and development; however, the ability of infants to biosynthesize long-chain fatty acids is unknown. This study explores the capacity of human infants to convert 18-carbon essential fatty acids to their elongated and desaturated forms, in vivo. A newly developed gas chromatography/negative chemical ionization/mass spectrometry method employing 2H-labeled essential fatty acids allowed assessment of this in vivo conversion with very high sensitivity and selectivity. Our results demonstrate that human infants have the capacity to convert dietary essential fatty acids administered enterally as 2H-labeled ethyl esters to their longer-chain derivatives, transport them to plasma, and incorporate them into membrane lipids. The in vivo conversion of linoleic acid (18:2n6) to arachidonic acid (20:4n6) is demonstrated in human beings. All elongases/desaturases necessary for the conversion of linolenic acid (18:3n3) to docosahexaenoic acid (22:6n3) are also active in the first week after birth. Although the absolute amounts of n-3 fatty acid metabolites accumulated in plasma are greater than those of the n-6 family, estimates of the endogenous pools of 18:2n6 and 18:3n3 indicate that n-6 fatty acid conversion rates are greater than those of the n-3 family. While these data clearly demonstrate the capability of infants to biosynthesize 22:6n3, a lipid that is required for optimal neural development, the amounts produced in vivo from 18:3n3 may be inadequate to support the 22:6n3 level observed in breast-fed infants.     

Influence of an n-6 Polyunsaturated Fatty Acid-Enriched Diet on the Development of Tolerance during Chronic Ethanol Administration in Rats

This study investigates the effects of n-6 polyunsaturated fatty acids (PUFAs), in the form of dietary Evening Primrose Oil (EPO) and safflower oil, on the development of tolerance to ethanol. The degree of fluorescence polarization of the fluoroprobes DPH, PROP-DPH, and TMA-DPH in isolated cortical synaptosomal membranes was measured. In addition, the development of tolerance, as shown by changes in synaptosomal membrane fluidity after an acute in vitro ethanol challenge, was also determined after 20 weeks of ethanol administration, either alone or together with a PUFA-enriched diet. Although the administration of EPO-enriched diet did not significantly render the inner core of the cortical synaptosomal membrane tolerant to the acute ethanol challenge, concomitant administration of ethanol and EPO was found to increase further the rigidity and tolerance to the acute ethanol challenge in the inner core. Chronic administration of safflower oil, which lacks γ-linolenic acid (18:3, n-6) but like EPO contains linoleic acid, either alone or together with chronic ethanol had no effect on synaptosomal membrane fluidity after an acute ethanol challenge. The results suggest that γ-linolenic acid or its metabolites may have an important role to play in the development of tolerance to chronic ethanol.     

Occurrence of individual trans-isomeric fatty acids in human myocardium, jejunum and aorta in relation to different degrees of atherosclerosis

With the aid of a highly selective capillary column coated with SP 2340, individual trans-fatty acids were identified in all tissue samples studied, the values being unrelated to the degree of atherosclerosis. The mean values of total trans-acids present in human myocardium, jejunum and aorta amounted to less than 1% of the total fatty acids. The trans-acid content was composed of traces of 9-trans-tetradecenoic acid and nearly equal amounts of 9-trans-hexadecenoate and trans-octadecenoate, the double bond in the latter occurring in the delta6, delta9 and delta11 positions. 9-trans,12-trans-octadecadienoate or the corresponding mixed geometric isomers could not be identified in any sample. Additionally, significant increases of 20:4c(n-6), 22:4c(n-6) and 22:6c(n-3) acids were measured in the myocardium of patients who had died from severe atherosclerosis of the aorta and coronary arteries. The atherosclerosis was not attributable to different dietary habits, as judged from the content of linoleic acid in their adipose tissue.     

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.     

Functional expression of a Delta12 fatty acid desaturase gene from spinach in transgenic pigs

Linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3) are polyunsaturated fatty acids that are essential for mammalian nutrition, because mammals lack the desaturases required for synthesis of Delta12 (n-6) and n-3 fatty acids. Many plants can synthesize these fatty acids and, therefore, to examine the effects of a plant desaturase in mammals, we generated transgenic pigs that carried the fatty acid desaturation 2 gene for a Delta12 fatty acid desaturase from spinach. Levels of linoleic acid (18:2n-6) in adipocytes that had differentiated in vitro from cells derived from the transgenic pigs were approximately 10 times higher than those from wild-type pigs. In addition, the white adipose tissue of transgenic pigs contained approximately 20% more linoleic acid (18:2n-6) than that of wild-type pigs. These results demonstrate the functional expression of a plant gene for a fatty acid desaturase in mammals, opening up the possibility of modifying the fatty acid composition of products from domestic animals by transgenic technology, using plant genes for fatty acid desaturases.     

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.     

Effect of dietary alpha-linolenic fatty acid derived from chia when fed as ground seed, whole seed and oil on lipid content and fatty acid composition of rat plasma

Coronary heart disease (CHD) is the most common cause of death in the Western world. In both the USA and the EU it accounts for over 600,000 deaths yearly. Early data showing the benefits n-3 fatty acids provide in preventing CHD disease were obtained using 20:5n-3 and 22:6n-3 fatty acids derived from fish. Recently, however, it has been shown that reduced risks of CHD and other cardiovascular diseases are found with 18:3n-3 fatty acid as well. To determine if 18:3n-3 fatty acids positively influence plasma composition, 32 male Wistar rats were fed ad libitum four isocaloric diets with the energy derived from corn oil (T(1)), whole chia seed (T(2)), ground chia seed (T(3)), or chia oil (T(4)) for 30 days. At the end of the feeding period the rats were sacrificed, and blood samples were analyzed to determine serum CHOL, HDL, LDL, TG content, hemogram, and fatty acid composition. Chia decreased serum TG content and increased HDL content. Only with the T(2) diet was TG significantly (p < 0.05) lower, and only with the T(3) diet was HDL significantly (p < 0.05) higher, than the control diet. Chia significantly (p < 0.05) increased the 18:3n-3, 20:5n-3 and 22:6n-3 plasma contents compared to the control diet, with no significant (p < 0.05) difference among chia diets detected. Significant (p < 0.05) improvement in n-6/n-3 fatty acid ratio was observed for all chia diets when compared to the control.