Effects of eicosatrienoic acid (20:3 n-9, Mead's acid) on some promalignant-related properties of three human cancer cell lines

The essential fatty acid deficiency (EFAD) is a metabolic condition related to cancer development. We studied the effect of eicosapentaenoic acid (EPA, 20:5 n-3) and eicosatrienoic acid (ETA, 20:3 n-9), an essential fatty acid (EFA) and non-EFA respectively, on tumour cells parameters linked to tumour progression and metastases. Human tumour cell lines (T-24 from urothelium, MCF-7 from breast and HRT-18 from colon) were used. EPA showed an anti-proliferative effect on the three lines. ETA showed the following effects: in T-24, the lipid peroxidation was decreased and E-cadherin was undetectable; in MCF-7, increased E-cadherin expression enhanced the lipid peroxidation and decreased cell proliferation; on HRT-18, the E-cadherin expression and lipid peroxidation diminished, whereas cell proliferation was increased. In conclusion, EFA (20:5 n-3) exhibited beneficial effects, whereas unusual ETA showed an opposite effect on some tumour parameters. The possible riskiness of EFA-deprivation, along with the potential of EFA as natural nutrapeutic products for human tumour prevention and treatment, makes EFA worthy of further consideration.     

Factors influencing fatty acid composition of common carp (Cyprinus carpio) muscle

There is evidence that n-3 highly unsaturated fatty acids (n-3 HUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for human health, especially for the cardiovascular system. The sources of n-3 HUFA, including EPA and DHA, are scarce in diet consumed by the Czech population. Thus, it would be beneficial to generally increase fish consumption and also to increase the content of the beneficial fatty acids (FA) in locally produced fish and other products. Therefore the overall aim of this paper was to review factors influencing lipid content and composition in common carp, which is the major cultured fish in the Czech Republic, and to identify long term sustainable ways for increasing the beneficial fatty acids in the carp flesh. We conclude that there are several ways to improve the FA composition of common carp in the traditional pond production. High amount of natural food, good supplemental diet containing high level of alpha-linolenic acid (ALA) and suitable processing and cooking were identified as the most important ones.     

Keloids in rural black South Africans. Part 2: dietary fatty acid intake and total phospholipid fatty acid profile in the blood of keloid patients

In the second part of this study, emphasis is placed on nutritional intakes (fatty acids and micronutrients) and fatty acid intake and metabolism in the blood, respectively, according to a combined 24 h recall and standardized food frequency questionnaire analyses of keloid prone patients (n=10), compared with normal black South Africans (n=80), and total phospholipid blood (plasma and red blood cell ) analyses of keloid patients (n=20), compared with normal individuals (n=20). Lipid extraction and fractionation by standard procedures, total phospholipid (TPL) separation with thin layer chromatography, and fatty acid methyl ester analyses with gas liquid chromatography techniques were used. Since nutrition may play a role in several disease disorders, the purpose of this study was to confirm or refute a role for essential fatty acids (EFAs) in the hypothesis of keloid formations stated in part 1 of this study. (1)According to the Canadian recommendation (1991), we observed that in keloid patients linoleic acid (LA) and arachidonic acid (AA) dietary intakes, as EFAs of the omega-6-series, are higher than the recommended 7-11 g/d. However, the a-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dietary intakes, as EFAs of the omega-3 series, are lower than the recommendation of 1.1-1.5 g/d. This was also the case in the control group, where a higher dietary intake of the omega-6 fatty acids and a slightly lower dietary intake of the omega-3 fatty acids occurred. Thus, we confirm a high dietary intake of LA (as a product of organ meats, diary products and many vegetable oils) and AA (as a product of meats and egg yolks), as well as lower dietary intakes of ALA (as a product of grains, green leafy vegetables, soy oil, rapeseed oil and linseed), and EPA and DHA (as products of marine oils). Lower micronutrient intakes than the recommended dietary allowances were observed in the keloid group that may influence EFA metabolism and/or collagen synthesis. Of cardinal importance may be the lower intake of calcium in the keloid patients that may contribute to abnormal cell signal transduction in fibroblasts and consequent collagen overproduction, and the lower copper intake that may influence the immune system, or perhaps even the high magnesium intake that stimulates metabolic activity. Micronutrient deficiencies also occurred in the diets of the normal black South Africans that served as a control group. In the case of plasma TPLs, deficiency of the omega-3 EFA series (ALA, EPA and DHA) occurred, and this is in accordance with the apparent lower omega-3 EFA intake in the diets of these patients. In the case of the red blood cell TPLs, as a true and reliable source of dietary fatty acid intake and metabolism, sufficient EFAs of the omega-6 series (LA and AA) and the omega-3 series (ALA, EPA and DHA) occurred. For this study group a relative deficiency of nutritional omega-3 EFA intake apparently did occur, but was probably compensated for by blood fatty acid metabolism.     

The delta 6 desaturase knock out mouse reveals that immunomodulatory effects of essential n-6 and n-3 polyunsaturated fatty acids are both independent of and dependent upon conversion

Typically fatty acids (FA) exert differential immunomodulatory effects with n-3 [α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and n-6 [linoleic acid (LA) and arachidonic acid (AA)] exerting anti- and pro-inflammatory effects, respectively. This over-simplified interpretation is confounded by a failure to account for conversion of the parent FA (LA and ALA) to longer-chain bioactive products (AA and EPA/DHA, respectively), thereby precluding discernment of the immunomodulatory potential of specific FA. Therefore, we utilized the Δ6-desaturase model, wherein knockout mice (D6KO) lack the Fads2 gene encoding for the rate-limiting enzyme that initiates FA metabolism, thereby providing a model to determine specific FA immunomodulatory effects. Wild-type (WT) and D6KO mice were fed one of four isocaloric diets differing in FA source (9 weeks): corn oil (LA-enriched), arachidonic acid single cell oil (AA-enriched), flaxseed oil (ALA-enriched) or menhaden fish oil (EPA/DHA-enriched). Splenic mononuclear cell cytokine production in response to lipopolysaccharide (LPS), T-cell receptor (TCR) and anti-CD40 stimulation was determined. Following LPS stimulation, AA was more bioactive compared to LA, by increasing inflammatory cytokine production of IL-6 (1.2-fold) and TNFα (1.3-fold). Further, LPS-stimulated IFNγ production in LA-fed D6KO mice was reduced 5-fold compared to LA-fed WT mice, indicating that conversion of LA to AA was necessary for cytokine production. Conversely, ALA exerted an independent immunomodulatory effect from EPA/DHA and all n-3 FA increased LPS-stimulated IL-10 production versus LA and AA. These data definitively identify specific immunomodulatory effects of individual FA and challenge the simplified view of the immunomodulatory effects of n-3 and n-6 FA.     

Fatty acid transfer from sow to piglet differs for different polyunsaturated fatty acids (PUFA)

Polyunsaturated fatty acids (PUFA) are essential for the development of the nervous system in animals. It is known that pigs are good models for human in many aspects. The aim of the study was to investigate how fat content and FA composition in sows' diet influence FA composition in brain of newborn and in liver and brain of one-day-old piglets, respectively. High fat (6 %) feeds were designed with regard to saturated or polyunsaturated fat content and n-6/n-3 ratio by adding either oats rich in linoleic acid (LA) or linseed oil rich in alpha-linolenic acid (ALA). The ratio n-6/n-3 PUFA was 11 in all three diets (the low fat (3 %), high fat saturated and high fat oats diet), while the ratio in the linseed oil diet was 2. Increased proportion of ALA in the diet increased ALA and eicosapentaenoic acid (EPA) in piglets' neutral and polar liver lipids and the long chain PUFA, EPA, docosapentaenoic and docosahexaenoic acid in piglet brain. The results suggest that transport of n-3 PUFA from sow to piglet was higher via milk than via bloodstream in the uterus and that increased content of ALA in sows' feed led to an increased accumulation of n-3 FA in piglets' liver and brain.     

Dietary ALA,EPA and DHA have distinct effects on oxylipin profiles in female and male rat kidney,liver and serum

There is much data on the effects of dietary n-3 fatty acids on tissue fatty acid compositions, but comparable comprehensive data on their oxygenated metabolites (oxylipins) is limited. The effects of providing female and male rats with diets high in α-linolenic acid (ALA), EPA or DHA for 6 weeks on oxylipins and fatty acids in kidney, liver and serum were therefore examined. The oxylipin profile generally reflected fatty acids, but it also revealed unique effects of individual n-3 fatty acids that were not apparent from fatty acid data alone. Dietary ALA increased renal and serum DHA oxylipins even though DHA itself did not increase, while dietary EPA did not increase DHA oxylipins in kidney or liver, suggesting that high EPA may inhibit this conversion. Oxylipin data generally corroborated fatty acid data that indicated that DHA can be retroconverted to EPA and that further retroconversion to ALA is limited. Dietary n-3 fatty acids decreased n-6 fatty acids and their oxylipins (except linoleic acid and its oxylipins), in order of effectiveness of DHA > EPA > ALA, with some exceptions: several arachidonic acid oxylipins modified at carbon 15 were not lower in all three sites, and EPA had a greater effect on 12-hydroxy-eicosatetraenoic acid and its metabolites in the liver. Oxylipins were predominantly higher in males, which was not reflective of fatty acids. Tissue-specific oxylipin profiles, therefore, provide further information on individual dietary n-3 fatty acid and sex effects that may help explain their unique physiological effects and have implications for dietary recommendations.     

Preferential accumulation of fatty acids in the testis and ovary of cultured and wild sweet smelt Plecoglossus altivelis

The effect of dietary lipid on the fatty acid composition of muscle, testis and ovary of cultured sweet smelt, Plecoglossus altivelis, was investigated and compared with that of wild sweet smelt. Cultured fish were fed three different diets for 12 weeks: a control diet rich in docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) (CO group); a diet deficient in DHA and EPA (DP group); and a diet rich in alpha-linolenic acid (ALA, 18:3n-3), but deficient in DHA and EPA (LP group). The fatty acid composition of muscle and gonad lipids was related with dietary fatty acids. Despite the difference in DHA and EPA content in the diets, muscles and gonads, respectively, contained almost equal levels of DHA and EPA in each CO and DP group. However, the muscle and gonad of the LP group showed a lower level of DHA than other groups, due to having the highest level of ALA. In the wild fish muscle, the DHA content was similar to that of CO and DP groups, but the EPA content showed the highest level in all groups. There was no difference in the muscle fatty acid proportions between male and female. On the other hand, the testes of cultured and wild fish were rich in DHA, EPA, docosapentaenoic acid and arachidonic acid, while ovaries were rich in oleic, palmitoleic, linoleic acids and ALA. Moreover, of all the groups, the fish fatty acid composition of the LP group was closest to that of wild fish. These results indicate that in the sweet smelt, tissue n-3 polyunsaturated fatty acids (PUFAs) greater than C20 can be synthesized from dietary precursors and special fatty acids are preferentially accumulated to the testis or ovary, respectively, to play different physiological functions.     

Metabolism of linoleic and α-linolenic acids in cultured cardiomyocytes: Effect of different N-6 and N-3 fatty acid supplementation

The metabolites of linoleic (LA) and -linolenic (ALA) acids are involved in coronary heart disease. Both n-6 and n-3 essential fatty acids (EFAs) are likely to be important in prevention of atherosclerosis since the common risk factors are associated with their reduced 6-desaturation. We previously demonstrated the ability of heart tissue to desaturate LA. In this study we examined the ability of cultured cardiomyocytes to metabolize both LA and ALA in vivo, in the absence and in the presence of gamma linolenic acid (GLA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) alone or combined together. In control conditions, about 25% of LA and about 90% of ALA were converted in PUFAs. GLA supplementation had no influence on LA conversion to more unsaturated fatty acids, while the addition of n-3 fatty acids, alone or combined together, significantly decreased the formation of interconversion products from LA. Using the combination of n-6 and n-3 PUFAs, GLA seemed to counterbalance partially the inhibitory effect of EPA and DHA on LA desaturation/elongation. The conversion of ALA to more unsaturated metabolites was greatly affected by GLA supplementation. Each supplemented fatty acid was incorporated to a significant extent into cardiomyocyte lipids, as revealed by gas chromatographic analysis. The n-6/n-3 fatty acid ratio was greatly influenced by the different supplementations; the ratio in GLA+EPA+DHA supplemented cardiomyocytes was the most similar to that recorded in control cardiomyocytes. Since important risk factors for coronary disease may be associated with reduced 6-desaturation of the parent EFAs, administration of n-6 or n-3 EFA metabolites alone could cause undesirable effects. Since they appear to have different and synergistic roles, only combined treatment with both n-6 and n-3 metabolites is likely to achieve optimum results.     

A mathematical model of fatty acid metabolism and VLDL assembly in human liver

The lipid composition of very-low-density lipoprotein (VLDL) in plasma is crucial for human health. A pre-requisite for the alteration of VLDL composition is a co-ordinated understanding of the complex interactions in VLDL assembly. In order to determine the potential effects of changes in substrate availability on VLDL lipid composition, we constructed, parameterized and evaluated a mechanistic mathematical model of the biosynthesis of triglycerides, phospholipids, and cholesterol esters and the assembly of VLDL in human hepatocytes. Using published data on human liver metabolism, the model was also used to provide insight into the complex process of lipid metabolism and to estimate the affinities of different liver enzymes for different fatty acids (FA). For example, we found that Delta6-desaturase is 19 times more selective for C18:3n-3 than C18:2n-6, stearoyl-CoA-desaturase is 2.7 times more selective for C18:0 than C16:0, Delta5-desaturase desaturates C20:4n-3 preferentially over C20:3n-6 and FA elongase preferentially elongates C18:3n-6. The model was also used to predict the plasma free fatty acid (FFA) composition required to generate a prescribed change in plasma lipoprotein FA composition. Furthermore, the model was tested against a published human feeding trial that investigated the effect of changes in dietary FA composition on human plasma lipid FA composition. The model is a useful tool for predicting the effect of changes in plasma FFA composition on plasma lipoprotein lipid FA composition.     

Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids

The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07–17.1 en%) and ALA (0.02–12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1–3 en% ALA and 1–2 en% LA but was suppressed to basal levels (～2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%).     

Compartmental modeling to quantify alpha-linolenic acid conversion after longer term intake of multiple tracer boluses

To estimate in vivo alpha-linolenic acid (ALA; C18:3n-3) conversion, 29 healthy subjects consumed for 28 days a diet providing 7% of energy from linoleic acid (C18:2n-6) and 0.4% from ALA. On day 19, subjects received a single bolus of 30 mg of uniformly labeled [(13)C]ALA and for the next 8 days 10 mg twice daily. Fasting plasma phospholipid concentrations of (12)C- and (13)C-labeled ALA, eicosapentaenoic acid (EPA; C20:5n-3), docosapentaenoic acid (DPA; C22:5n-3), and docosahexaenoic acid (DHA; C22:6n-3) were determined on days 19, 21, 23, 26, 27, and 28. To estimate hepatic conversion of n-3 fatty acids, a tracer model was developed based on the averaged (13)C data of the participants. A similar tracee model was solved using the averaged (12)C values, the kinetic parameters derived from the tracer model, and mean ALA consumption. ALA incorporation into plasma phospholipids was estimated by solving both models simultaneously. It was found that nearly 7% of dietary ALA was incorporated into plasma phospholipids. From this pool, 99.8% was converted into EPA and 1% was converted into DPA and subsequently into DHA. The limited incorporation of dietary ALA into the hepatic phospholipid pool contributes to the low hepatic conversion of ALA into EPA. A low conversion of ALA-derived EPA into DPA might be an additional obstacle for DHA synthesis.     

Inhibition of Δ-6 desaturase reduces fatty acid re-esterification in 3T3-L1 adipocytes independent of changes in n3-PUFA cellular content

Δ-6 desaturase (D6D) is a key enzyme in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFA). Evidence suggests that reduced D6D activity not only disrupts LC-PUFA production, but also impacts whole body lipid handling and body weight; however, the mechanisms remain largely unexplored. Therefore, we investigated the effect of D6D inhibition on the regulation of lipid accumulation in 3T3-L1 adipocytes with and without changes in n-3 PUFA content. 3T3-L1 cells were treated with a D6D inhibitor (SC-26196) in the presence or absence of α-linolenic acid (ALA) throughout differentiation. We found that D6D inhibition blocked the conversion of ALA to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPAn-3) when ALA was supplemented, while no changes in n-3 PUFA content were observed in cells treated with the D6D inhibitor alone. D6D inhibited cells had reduced triacylglycerol (TAG) accumulation despite an EPA/DPA deficiency. In addition, analyses of cellular protein markers, as well as non-esterified fatty acids and glycerol release in medium, suggested an increase in lipolysis and a decrease in fatty acid re-esterification in D6D-inhibited cells, independent of n-3 PUFA changes. To provide further evidence, we treated cells with the D6D inhibitor in the presence or absence of EPA and compared them with ALA-treated cells. Although EPA further reduced TAG content, the reduced markers of fatty acid re-esterification were not affected by ALA or EPA. Collectively, this study provides new insight showing that D6D inhibition reduces TAG accumulation and fatty acid re-esterification in adipocytes independent of changes in n-3 PUFA cellular content.     

Developmental changes in the fatty acids of rat uterus and the influence of dietary essential fatty acids.

The effect of age on uterine fatty acid composition was studied in rats fed diets of differing fatty acid composition. Uteri of newly weaned 23-day rats had a higher fatty acid content and a higher proportion of short-chain (less than or equal to C18) fatty acids. Higher incorporation of C less than or equal to 18 fatty acids into neutral lipid (NL) and phospholipid (PL) of young 42-day rats compared with adult 240-day rats was detected. Uterine NL incorporated predominantly C less than or equal to 18 fatty acids which may be an important metabolic energy store in developing uterine tissue. Incorporation of C less than or equal to 18 fatty acids by uterine PL and NL was relatively unselective. In contrast, there was selective retention of arachidonic acid (AA) and docosahexanoic acid (DHA) throughout uterine development. An effect of dietary EFA on uterine n-3 and n-6 EFA was detected in each age group. There was marked retention of uterine AA when dietary supplies of n-6 EFA were low, but the total AA, eicosapentaenoic acid (EPA) and DHA in uterine PL remained constant in the three diet groups, and a constant content of AA, EPA and DHA was maintained throughout uterine development, regardless of diet. The degree of n-3 substitution achieved in this study inhibited uterine release of PG and parturition in adult rats.     

Reversibility of the changes induced by n-3 fatty acids in mouse plasma, liver and blood cell lipids

The changes induced by dietary n-3 fatty acids (FA) in the lipids and FA of plasma, liver and blood cells, and their reversibility, was studied in mice given a diet containing 9% fish oil (FO) for 2 weeks and then returned to, and kept for another 2 weeks on, the usual standard lab chow diet. In plasma, the concentrations of phospholipids (PL), mostly phosphatidylcholine (PC), triacylglycerols (TG), cholesterol and cholesterol esters (CE) decreased rapidly after starting the FO diet, and remained low from day 3 onwards. This decrease was concomitant with a remarkable reduction in the n-6 FA, especially 18:2n-6, not compensated for by the relative enrichment in n-3 FA induced by FO. In liver, TG and CE decreased and PL slightly increased, all of them showing reduced n-6/n-3 ratios. Sphingomyelin, which lacks polyunsaturated FA other than small amounts of 18:2 and 24:2n-6, showed altered ratios between its very long chain monoenes and saturates. In the washout phase, the most rapid event was an immediate increase in 18:2n-6 and after a few days in 20:4n-6 in plasma and liver, where most of the lipid and FA changes were reversed completely in about 10 days. In the case of blood cells even 2 weeks were insufficient for a reversal to the initial n-6/n-3 ratios. The lipid class responsible for this lack of reversibility was phosphatidylethanolamine, PC having returned to the initial fatty acid composition during the stated period.     

Bio-availability and metabolism of n-3 fatty acid rich garden cress (Lepidium sativum) seed oil in albino rats

The ratio of fatty acids namely linoleic acid (LA, 18:2, n-6) and alpha linolenic acid (ALA, 18:3, n-3) in the diet plays an important role in enrichment of ALA in tissues and further conversion to long-chain polyunsaturated fatty acids (LC-PUFA) like eicosapentaenoic acid (EPA, 20:5, n-3) and docosahexaenoic acid (DHA, 22:6, n-3). Garden cress seed oil (GCO) is one of the richest sources of omega-3 fatty acid and contains 29-34.5% of ALA. In this study, dietary supplementation of GCO on bio-availability and metabolism of alpha-linolenic acid was investigated in growing rats. Male wistar rats were fed with semi-purified diets supplemented with 10.0% sunflower oil (SFO 10%); 2.5% GCO and 7.5% SFO (GCO 2.5%); 5% GCO and 5% SFO (GCO 5.0%); 10% GCO (GCO 10%) for a period of 8 weeks. There was no significant difference with regard to the food intake, body weight gain and organ weights of rats in different dietary groups. Rats fed with GCO showed significant increase in ALA levels in serum and tissues compared to SFO fed rats. Feeding rats with 10% GCO lowered hepatic cholesterol by 12.3% and serum triglycerides by 40.4% compared to SFO fed group. Very low density lipoprotein cholesterol (VLDL-C) and low density lipoprotein cholesterol (LDL-C) levels decreased by 9.45% in serum of 10% GCO fed rats, while HDL remained unchanged among GCO fed rats. Adipose tissue showed incorporation of 3.3-17.4% of ALA and correlated with incremental intake of ALA. Except in adipose tissue, the EPA, DHA levels increased significantly in serum, liver, heart and brain tissues in GCO fed rats. A maximum level of DHA was registered in brain (11.6%) and to lesser extent in serum and liver tissues. A significant decrease in LA and its metabolite arachidonic acid (AA) was observed in serum and liver tissue of rats fed on GCO. Significant improvement in n-6/n-3 fatty acid ratio was observed in GCO based diets compared to diet containing SFO. This is the first study to demonstrate that supplementation of GCO increases serum and liver ALA, EPA, DHA and decreases LA and AA in rats. Therefore, the GCO can be considered as a potential, alternate dietary source of ALA.     

Direct transesterification of plasma fatty acids for the diagnosis of essential fatty acid deficiency in cystic fibrosis

This study was aimed at redefining criteria for essential fatty acid (EFA) deficiency with the use of the direct transesterification procedure (1986. J. Lipid Res. 27: 114-120) and at determining whether a simple assay of total fatty acids (FA) is as predictive of EFA deficiency as the FA pattern from plasma, red cell, and platelet phospholipids. Fasting blood samples were taken from 163 cystic fibrosis (CF) patients who were encouraged to consume 35-40% of their calories as fat. Their mean (+/- SD) age was 9.6 +/- 4.8 yr. The control group consisted of 44 unaffected siblings aged 13.1 +/- 3.1 yr. The 20:3(n-9)/20:4(n-6) ratio in 77 (47%) CF children was more than 2 SD above the values (mean +/- SD) of 0.021 +/- 0.007 obtained in the 44 controls. Groups of EFA-sufficient (n = 10) and EFA-deficient (n = 7) subjects were selected for further studies. The plasma total FA 20:3(n-9)/20:4(n-6) ratios of 0.029 +/- 0.003 in EFA-sufficient and of 0.216 +/- 0.103 in EFA-deficient was as good a discriminant as FA in phospholipids from plasma, red cell PC, and platelets. Among the 21 individual fatty acids, 20:3(n-9), which was also found in controls, and 16:1(n-7) (palmitoleic) proved to be the most sensitive indices of EFA deficiency. They are equally reliable in plasma, red cells, and platelets, but the inverse linear relationship (r = -0.91) between the n-7 family and 18:2(n-6) proved to be more closely associated with EFA deficiency than the one (r = 0.66) between 20:3(n-9) and 20:4(n-6).(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlations between blood and tissue omega-3 LCPUFA status following dietary ALA intervention in rats

The aim of this study was to assess relationships between the fatty acid contents of plasma and erythrocyte phospholipids and those in liver, heart, brain, kidney and quadriceps muscle in rats. To obtain a wide range of tissue omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFA) we subjected weanling rats to dietary treatment with the n-3 LCPUFA precursor, alpha linolenic acid (ALA, 18:3 n-3) for 3 weeks. With the exception of the brain, we found strong and consistent correlations between the total n-3 LCPUFA fatty acid content of both plasma and erythrocyte phospholipids with fatty acid levels in all tissues. The relationships between eicosapentaenoic acid (EPA, 20:5 n-3) and docosapentaenoic acid (DPA, 22:5 n-3) content in both blood fractions with levels in liver, kidney, heart and quadriceps muscle phospholipids were stronger than those for docosahexaenoic acid (DHA, 22:6 n-3). The strong correlations between the EPA+DHA (the Omega-3 Index), total n-3 LCPUFA and total n-3 PUFA contents in both plasma and erythrocyte phospholipids and tissues investigated in this study suggest that, under a wide range of n-3 LCPUFA values, plasma and erythrocyte n-3 fatty acid content reflect not only dietary PUFA intakes but also accumulation of endogenously synthesised n-3 LCPUFA, and thus can be used as a reliable surrogate for assessing n-3 status in key peripheral tissues.     

Maternal dietary fat alters amniotic fluid and fetal intestinal membrane essential n-6 and n-3 fatty acids in the rat

We investigated whether maternal fat intake alters amniotic fluid and fetal intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% alpha-linolenic acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n-6) levels in the n-3-deficient group than in the control group (DHA: 1.29 +/- 0.10 and 6.29 +/- 0.33 g/100 g fatty acid; DPA: 4.01 +/- 0.35 and 0.73 +/- 0.15 g/100 g fatty acid, respectively); these differences in DHA and DPA were present in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal intestines in the n-3-deficient group had significantly higher LA, arachidonic acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty acid ratio was 4.9 +/- 0.2 and 32.2 +/- 2.1 in PC and 2.4 +/- 0.03 and 17.1 +/- 0.21 in PE in n-3-deficient and control group intestines, respectively. We demonstrate that maternal dietary fat influences amniotic fluid and fetal intestinal membrane structural lipid essential fatty acids. Maternal dietary fat can influence tissue composition by manipulation of amniotic fluid that is swallowed by the fetus or by transport across the placenta.     

Metabolic switching of human myotubes is improved by n-3 fatty acids

The aim of the present study was to examine whether pretreatment with different fatty acids, as well as the liver X receptor (LXR) agonist T0901317, could modify metabolic switching of human myotubes. The n-3 FA eicosapentaenoic acid (EPA) increased suppressibility, the ability of glucose to suppress FA oxidation. Substrate-regulated flexibility, the ability to increase FA oxidation when changing from a high glucose, low fatty acid condition (“fed”) to a high fatty acid, low glucose (“fasted”) condition, was increased by EPA and other n-3 FAs. Adaptability, the capacity to increase FA oxidation with increasing FA availability, was enhanced after pretreatment with EPA, linoleic acid (LA), and palmitic acid (PA). T0901317 counteracted the effect of EPA on suppressibility and adaptability, but it did not affect these parameters alone. EPA per se accumulated less, however, EPA, LA, oleic acid, and T0901317 treatment increased the number of lipid droplets (LD) in myotubes. LD volume and intensity, as well as mitochondrial mass, were independent of FA pretreatment. Microarray analysis showed that EPA regulated more genes than the other FAs and that specific pathways involved in carbohydrate metabolism were induced only by EPA. The present study suggests a favorable effect of n-3 FAs on skeletal muscle metabolic switching and glucose utilization.