The FADS1 Genotype Modifies Metabolic Responses to the Linoleic Acid and Alpha-linolenic Acid Containing Plant Oils-Genotype Based Randomized Trial FADSDIET2.

SCOPE: The article investigates the FADS1 rs174550 genotype interaction with dietary intakes of high linoleic acid (LA) and high alpha-linolenic acid (ALA) on the response of fatty acid composition of plasma phospholipids (PLs), and of markers of low-grade inflammation and glucose-insulin homeostasis. METHODS AND RESULTS: One-hundred thirty homozygotes men for FADS1 rs174550 SNP (TT and CC genotypes) were randomized to an 8-week intervention with either LA- or ALA-enriched diet (13 E% PUFA). The source of LA and ALA are 30-50 mL of sunflower oil (SFO, 62-63% LA) and Camelina sativa oil (CSO, 30- are randomized to an 35% ALA), respectively. In the SFO arm, there is a significant genotype x diet interaction for the proportion of arachidonic acid in plasma phospholipids (p < 0.001), disposition index (DI30 ) (p = 0.039), and for serum high-sensitive c-reactive protein (hs-CRP, p = 0.029) after excluding the participants with hs-CRP concentration of >10 mg L-1 and users of statins or anti-inflammatory therapy. In the CSO arm, there are significant genotype x diet interactions for n-3 polyunsaturated fatty acids, but not for the clinical characteristics. CONCLUSIONS: The FADS1 genotype modifies the response to high PUFA diets, especially to high-LA diet. These findings suggest that approaches considering FADS variation may be useful in personalized dietary counseling.

Dietary docosahexaenoic acid inhibits neurodegeneration and prevents stroke.

Stroke severely impairs quality of life and has a high mortality rate. On the other hand, dietary docosahexaenoic acid (DHA) prevents neuronal damage. In this review, we describe the effects of dietary DHA on ischemic stroke-associated neuronal damage and its role in stroke prevention. Recent epidemiological studies have been conducted to analyze stroke prevention through DHA intake. The effects of dietary intake and supply of DHA to neuronal cells, DHA-mediated inhibition of neuronal damage, and its mechanism, including the effects of the DHA metabolite, neuroprotectin D1 (NPD1), were investigated. These studies revealed that DHA intake was associated with a reduced risk of stroke. Moreover, studies have shown that DHA intake may reduce stroke mortality rates. DHA, which is abundant in fish oil, passes through the blood-brain barrier to accumulate as a constituent of phospholipids in the cell membranes of neuronal cells and astrocytes. Astrocytes supply DHA to neuronal cells, and neuronal DHA, in turn, activates Akt and Raf-1 to prevent neuronal death or damage. Therefore, DHA indirectly prevents neuronal damage. Furthermore, NDP1 blocks neuronal apoptosis. DHA, together with NPD1, may block neuronal damage and prevent stroke. The inhibitory effect on neuronal damage is achieved through the antioxidant (via inducing the Nrf2/HO-1 system) and anti-inflammatory effects (via promoting JNK/AP-1 signaling) of DHA.

Effect of nanoemulsion particle size on the bioavailability and bioactivity of perilla oil in rats.

The aim of this study was to investigate the bioavailability and bioactivity of perilla (Perilla frutescens) oil nanoemulsions prepared at different homogenization pressures by measuring the weight, fatty acid profile, and antioxidant and anti-inflammatory properties in rats. The high-pressure homogenization significantly reduced the particle size of perilla oil nanoemulsions and enhanced their stability, and the minimum particle size was 293.87 ± 6.55 nm at 120 MPa. There was an increase in the weight and fatty acid levels in the plasma and liver of test group rats. The highest glutathione (GSH) and the lowest malondialdehyde (MDA) levels of 18.76 ± 10.51 mg GSH/g prot and 20.27 ± 2.46 nmol/mg prot, respectively, were recorded in rats administrated perilla oil nanoemulsions prepared at 120 MPa. However, there was no significant difference in superoxide dismutase activity (SOD) between the groups. The interferon-gamma (IL-γ), interleukin-1 beta (IL-1ß), IL-6 (interleukin-6), and IL-8 (interleukin-8) levels in the test groups were lower than those in the blank and control groups at 8 hr after lipopolysaccharide injection. The IL-1ß, IL-6, and IL-8 levels were 49.52 ± 14.06, 90.13 ± 6.04, and 419.71 ± 32.03 ng/L, respectively, in rats treated with perilla oil nanoemulsions prepared at 120 MPa. Both perilla oil and its nanoemulsions decreased estradiol levels and damaged the ovaries. Overall, our findings show that the test nanoemulsions enhanced the bioavailability of perilla oil, which resulted in enhanced antioxidant and anti-inflammatory responses; thus, we provide a new approach to deliver perilla oil. PRACTICAL APPLICATION: Nanoemulsions can be used to deliver drugs and bioactive compounds, and perilla oil nanoemulsions can be used in healthcare products and beverage industries.

EPA+DHA, but not ALA, Improved Lipids and Inflammation Status in Hypercholesterolemic Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.

SCOPE: To compare the effects of supplementary eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) versus α-linolenic acid (ALA) on lipid profiles, inflammatory status, and fatty acid composition of peripheral blood mononuclear cells (PBMCs) in hypercholesterolemic adults. METHODS AND RESULTS: A randomized, controlled, double-blind trial is conducted to examine the effects of consumption of control oil, 4.2 g/d ALA, 7.2 g/d ALA, 1.8 g/d DHA+EPA, or 3.6 g/d EPA+DHA for 12 weeks on lipid profiles, fatty acid composition of PBMCs and in vitro production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by PBMCs in 123 subjects with hypercholesteremia. After the intervention, subjects who receive a low and high dose of DHA/EPA experience 11.99% and 15.78% decreases in triglycerides which is significantly different from that of the control group (p < 0.05). The in vitro study indicates that supplementation of high-dose DHA+EPA induces the greatest decrease of IL-6 production by PBMCs relative to other groups (p = 0.046). ALA intervention significantly increases the PBMCs composition of ALA but not EPA/DHA. CONCLUSION: EPA+DHA, but not ALA, improves lipids and inflammation status in hypercholesterolemic adults. Supplementation of ALA does not increase the PBMCs composition of EPA/DHA in middle-aged to elderly Chinese.

Effect of 1- and 2-Month High-Dose Alpha-Linolenic Acid Treatment on 13 C-Labeled Alpha-Linolenic Acid Incorporation and Conversion in Healthy Subjects.

SCOPE: The study aims at identifying 1) the most sensitive compartment among plasma phospholipids, erythrocytes, and LDL for studying alpha-linolenic acid (ALA) conversion, and 2) whether ALA incorporation and conversion is saturable after administration of 13 C-labeled ALA-rich linseed oil (LO). The effect of a daily intake of 7 g nonlabeled LO (>43% w/w ALA) for 1 month after bolus administration of 7 g 13 C-labeled LO on day 1, and for 2 months after bolus administration of 7 g 13 C-labeled LO on day 1 and day 29 on 13 C-ALA incorporation and conversion into its higher homologs is investigated in healthy volunteers. METHODS AND RESULTS: Incorporation and conversion of LO-derived 13 C-labeled ALA is quantified by applying compartmental modeling. After bolus administration, a fractional conversion of approximately 30% from 13 C-ALA to 13 C-DHA is calculated as reflected by the LDL compartment. Treatment with LO for 8 weeks induces a mean reduction of 13 C-ALA conversion to 13 C-DHA by 48% as reflected by the LDL compartment, and a mean reduction of the 13 C-ALA incorporation into LDL by 46%. CONCLUSION: A 2-month dietary intake of a high dose of LO is sufficient to reach saturation of ALA incorporation into LDL particles, which are responsible for ALA distribution in the body.

Maternal liver docosahexaenoic acid (DHA) stores are increased via higher serum unesterified DHA uptake in pregnant long Evans rats.

Maternal docosahexaenoic acid (DHA, 22:6n-3) supplies the developing fetus during pregnancy; however, the mechanisms are unclear. We utilized pregnant rats to determine rates of DHA accretion, tissue unesterified DHA uptake and whole-body DHA synthesis-secretion. Female rats maintained on a DHA-free, 2% α-linolenic acid diet were either:1) sacrificed at 56 days for baseline measures, 2) mated and sacrificed at 14-18 days of pregnancy or 3) or sacrificed at 14-18 days as age-matched virgin controls. Maternal brain, adipose, liver and whole body fatty acid concentrations was determined for balance analysis, and kinetic modeling was used to determine brain and liver plasma unesterified DHA uptake and whole-body DHA synthesis-secretion rates. Total liver DHA was significantly higher in pregnant (95±5 µmol) versus non-pregnant (49±5) rats with no differences in whole-body DHA synthesis-secretion rates. However, liver uptake of plasma unesterified DHA was 3.8-fold higher in pregnant animals compared to non-pregnant controls, and periuterine adipose DHA was lower in pregnant (0.89±0.09 µmol/g) versus non-pregnant (1.26±0.06) rats. In conclusion, higher liver DHA accretion during pregnancy appears to be driven by higher unesterified DHA uptake, potentially via DHA mobilization from periuterine adipose for delivery to the fetus during the brain growth spurt.

The nutraceutical potential of omega-3 alpha-linolenic acid in reducing the consequences of stroke.

Stroke is a worldwide major cause of mortality and morbidity. Preclinical studies have identified over 1000 molecules with brain-protective properties. More than 200 clinical trials have evaluated neuroprotective candidates for ischemic stroke yet, to date almost all failed, leading to a re-analysis of treatment strategies against stroke. An emerging view is to seek combinatory therapy, or discovering molecules able to stimulate multiple protective and regenerative mechanisms. A pertinent experimental approach to identify such candidates is the study of brain preconditioning, which refers to how the brain protects itself against ischemia and others stress-inducing stimuli. The recent discovery that nutrients like alpha-linolenic acid (ALA is an essential omega-3 polyunsaturated fatty acid required as part of our daily diet), may be an efficient brain preconditionner against stroke fosters the novel concept of brain preconditioning by nutraceuticals. This review stresses the underestimated role of nutrition in preventing and combating stroke. Although there is a consensus that increased consumption of salt, fatty foods and alcoholic beverages may promote pathologies like hypertension, obesity and alcoholism - all of which are well known risk factors of stroke - few risk factors are attributed to a deficiency in an essential nutrient in the diet. The ALA deficiency observed in the Western modern diets may itself constitute a risk factor. This review outlines how ALA supplementation by modification of the daily diet prevented mortality and cerebral damage in a rodent model of ischemic stroke. It also describes the pleiotropic ability of ALA to trigger responses that are multicellular, mechanistically diverse, resulting in neuronal protection, stimulation of neuroplasticity, and brain artery vasodilation. Overall, this review proposes a promising therapeutic opportunity by integrating a nutritional-based approach focusing on enriching the daily diet in ALA to prevent the devastating damage caused by stroke.

Oral Absorption and Disposition of alpha-Linolenic, Rumenic and Vaccenic Acids After Administration as a Naturally Enriched Goat Dairy Fat to Rats.

Although there is extensive information describing the positive biological effects of conjugated linoleic acid and its main isomer rumenic acid (RA; C18:2 cis 9, trans 11), and alpha-linolenic acid (ALA) and vaccenic acid (TVA), data about their bioavailability are not available. In this work, we investigated the oral absorption and disposition of these fatty acids in Wistar rats. A naturally enriched goat dairy fat (EDF) was obtained by supplementing ruminant diets with oils or oilseeds rich in polyunsaturated fatty acids (PUFA). The EDF was administered orally (single dose of 3000 mg EDF/kg body weight equivalent to 153 mg TVA/kg body weight, 46 mg RA/kg body weight and 31 mg ALA/kg body weight), and serial blood and liver samples were collected and TVA, RA and ALA concentrations determined by GC/MS. The fatty acids TVA, RA and ALA were rapidly absorbed (t1/2a, 0.36, 0.66 and 0.76 h, respectively, for plasma) and slowly eliminated (t1/2ß, 17.04, 18.40 and 16.52 h, respectively, for plasma). The maximum concentration (C max) was detected in liver > plasma > erythrocyte. Our study shows that when orally administered EDF, its components TVA, RA and ALA were rapidly absorbed and distributed throughout the body by the blood circulation to exert systemic effects.

Impact of various emulsifiers on ALA bioavailability and chylomicron synthesis through changes in gastrointestinal lipolysis.

Formulating healthy food rich in omega 3 fatty acids requires prior knowledge of the parameters influencing their bioavailability and their metabolic fate. In this context, we studied the effects of various emulsifiers widely used in the food industry, on the gastrointestinal lipolysis of flaxseed oil emulsions in an in vitro model and on the intestinal absorption and lymphatic secretion of alpha-linolenic acid (ALA) in rats. In vitro data showed that the emulsification of flaxseed oil with soya lecithin improved the gastric lipolysis of the oil (+30%), while the presence of Tween 80 or of sodium caseinate decreased it (-80% and -40%, respectively). The in vivo data demonstrated that the intestinal absorption and the lymphatic secretion of ALA were improved with soya lecithin (Cmax = 24 mg mL(-1)) and reduced in the presence of sodium caseinate (Cmax = 7 mg mL(-1)) compared to unemulsified flaxseed oil (Cmax = 16 mg mL(-1)); Tween 80 had no effect. In addition, the synthesized chylomicrons were notably larger and more numerous with soya lecithin whereas they were smaller in the presence of sodium caseinate (p < 0.05). This study shows that the intestinal bioavailability of ALA was increased by the emulsification of flaxseed oil with soya lecithin via an improved lipolysis, favouring the intestinal absorption of ALA and the secretion of many large chylomicrons in lymph.

Modulatory effects of alpha-linolenic acid on generation of reactive oxygen species in elaidic acid enriched peritoneal macrophages in rats.

Fatty acids are known to influence the ability of macrophages to generate reactive oxygen species (ROS). However the effect of elaidic acid (EA, 18:1 trans fatty acid) on ROS generation is not well studied. Rat peritoneal macrophages were enriched with elaidic acid by incubating the cells with 80 1M EA. The macrophages containing EA generated higher amounts of superoxide anion (O2*-), hydrogen peroxide (H2O2) and nitric oxide (NO) by 54, 123 and 237%, respectively as compared to control cells which did not contain EA. To study the competition of other C18 fatty acids with EA macrophages were incubated with EA along with stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2) and alpha-linolenic acid (ALA, 18:3). ALA significantly reduced the incorporation of EA into macrophage lipids. This also significantly reduced the generation of O2*-, H2O2, NO by macrophages. Studies were also conducted by feeding rats with diet containing partially hydrogenated vegetable fat (PHVF) as a source for EA and linseed oil (LSO) as a source for ALA. The rats were fed AIN-93 diet containing PHVF with 17% EA and incremental amounts of linseed oil for 10 weeks. The peritoneal macrophages from rats fed partially hydrogenated vegetable fat generated higher levels of O2*-, H2O2, NO by 46, 161 and 76% respectively, when compared to rats fed control diets containing ground nut oil. Macrophages from rats fed PHVF with incremental amounts of LSO produced significantly lower levels ROS in a dose dependent manner. Thus ALA reduces the higher levels of ROS generated by macrophages containing EA.

α-Linolenic acid: nutraceutical, pharmacological and toxicological evaluation.

α-Linolenic acid (ALA), a carboxylic acid with 18 carbons and three cis double bonds, is an essential fatty acid needed for human health and can be acquired via regular dietary intake of foods that contain ALA or dietary supplementation of foods high in ALA, for example flaxseed. ALA has been reported to have cardiovascular-protective, anti-cancer, neuro-protective, anti-osteoporotic, anti-inflammatory, and antioxidative effects. ALA is the precursor of longer chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), but its beneficial effects on risk factors for cardiovascular diseases are still inconclusive. The recommended intake of ALA for cardiovascular health is reported to be 1.1-2.2g/day. Although there are limited toxicological data for ALA, no serious adverse effects have been reported. The evidence on an increased prostate cancer risk in association with dietary ALA is not conclusive. Based on the limited data currently available, it may be concluded that ALA may be beneficial as a nutraceutical/pharmaceutical candidate and is safe for use as a food ingredient.

Lymphatic transport of α-linolenic acid and its conversion to long chain n-3 fatty acids in rats fed microemulsions of linseed oil.

In the present study we evaluated the uptake of ALA and its conversion to EPA + DHA in rats given linseed oil (LSO) in native form or as a microemulsion in whey protein or in lipoid. In a single oral dose study in which rats maintained on rodent pellets deficient in ω-3 fatty acids were intubated with 0.35 g LSO in lipoid, the amount of ALA present in lymph was increased reaching a maximum concentration of 16.23 mg/ml at 2.5 h. The amount of ALA present in lymph was increased to a maximum level of 10.95 mg/ml at 4 h in rats given LSO as a microemulsion in whey protein. When LSO was given without emulsification, the amount of ALA present in lymph was found to reach a maximum level of 7.08 mg/ml at 6 h. A similar result was observed when weaning rats were intubated with 0.15 g of LSO per day for a period of 60 days. Higher levels of ALA by 41 and 103 % were observed in lymph lipids of rats given microemulsions of LSO in whey protein and in lipoid respectively as compared to rats given LSO without pre-emulsification. Very little conversion of ALA to EPA and DHA was observed in lymph lipids but higher amounts of EPA + DHA was observed in liver and serum of rats given LSO in microemulsion form. This study indicated that ALA concentration in lymph lipids was increased when LSO was given in microemulsion form in lipoid and further conversion to EPA and DHA was facilitated in liver and serum.

Effects of urea formaldehyde condensation polymer treatment of flaxseed on ruminal digestion and lactation in dairy cows.

Flaxseed is a potent source of the n-3 fatty acid α-linolenic acid (ALA), yet most ALA is lost during ruminal biohydrogenation when ground flaxseed is fed to ruminants. Heat processing and urea formaldehyde condensation polymer (UFCP) treatment of flaxseed were investigated as possible means of protecting ALA from ruminal degradation. Ground flaxseed (GF), heated ground flaxseed (HGF), or UFCP-treated ground flaxseed (UFCPGF) were incubated for 0, 4, 8, and 12h in 4 ruminally cannulated multiparous lactating Holstein cows. Compared with GF, HGF and UFCPGF decreased ruminal disappearance of dry matter, crude protein, and ALA. Pepsin-digestible protein remaining after 12h of ruminal incubation was greater for UFCPGF and HGF than for GF. Twenty-four lactating Holstein cows (207 ± 37 d in milk, 668 ± 66 kg of body weight, and 1.33 ± 0.56 lactations) were then used in a randomized complete block design experiment with a basal feeding period to assess effects of flaxseed treatment on ALA enrichment of plasma and milk as well as lactational performance. No evidence existed that supplementation of HGF and UFCPGF affected dry matter intake, milk fat content, milk protein content, or energy-corrected milk yield, but UFCPGF marginally decreased milk yield compared with HGF. Plasma concentration of ALA was not affected by treatment. Concentrations of n-3 fatty acids and conjugated linoleic acids in milk fat were increased by UFCPGF relative to HGF, but ALA yield was not affected. Taken together, in situ results suggest that heat-treated flaxseed, with or without UFCP treatment, slowed ruminal disappearance of ALA. Feeding UFCP-treated flaxseed failed to alter ALA content of plasma or milk ALA yield relative to heating alone.

Papel de los ácidos grasos omega-3 en la prevención de enfermedades cardiovasculares / Role of omega-3 fatty acids in cardiovascular disease prevention

Los ácidos grasos, además de su conocido valor energético y su función estructural, presentan otro tipo de propiedades beneficiosas. En concreto, los ácidos grasos poliinsaturados omega-3 actúan sobre el aparato cardiovascular a través de multitud de vías ejerciendo un efecto protector frente al riesgo cardiovascular. Los beneficios asociados a la reducción de la mortalidad cardiaca y en concreto la muerte súbita, están relacionados con la incorporación de EPA y DHA en los fosfolípidos de la membrana de los cardiomiocitos. Se ha establecido un índice que relaciona el porcentaje de EPA+DHA del total de ácidos grasos en los eritrocitos y riesgo de muerte por enfermedad cardiovascular pudiendo estratificarlo en diferentes grados. Por lo tanto, el pescado graso principal fuente de AGPI w-3, se comporta como alimento de referencia en las dietas cardiosaludables (AU)

Fatty acids, in addition to its known energy value and its structural function, have other beneficial properties. In particular, the polyunsaturated fatty acids omega-3 acting on the cardiovascular apparatus through many channels exerting a protective effect against cardiovascular risk. The benefits associated with the reduction in cardiac mortality and sudden death particular, are related to the incorporation of EPA and DHA in phospholipid membrane of cardiomyocytes. An index is established that relates the percentage of EPA + DHA of total fatty acids in erythrocytes and risk of death from cardiovascular disease may layering in different degrees. Therefore, the primary source of fatty fish w-3 PUFA, behaves like a reference food in cardiosaludables diets (AU)

Lymphatic absorption of α-linolenic acid in rats fed flaxseed oil-based emulsion.

The bioavailability of α-linolenic acid (ALA) from flaxseed oil in an emulsified form v. a non-emulsified form was investigated by using two complementary approaches: the first one dealt with the characterisation of the flaxseed oil emulsion in in vitro gastrointestinal-like conditions; the second one compared the intestinal absorption of ALA in rats fed the two forms of the oil. The in vitro study on emulsified flaxseed oil showed that decreasing the pH from 7·3 to 1·5 at the physiological temperature (37°C) induced instantaneous oil globule coalescence. Some phase separation was observed under acidic conditions that vanished after further neutralisation. The lecithin used to stabilise the emulsions inhibited TAG hydrolysis by pancreatic lipase. In contrast, lipid solubilisation by bile salts (after lipase and phospholipase hydrolysis) was favoured by preliminary oil emulsification. The in vivo absorption of ALA in thoracic lymph duct-cannulated rats fed flaxseed oil, emulsified or non-emulsified, was quantified. Oil emulsification significantly favoured the rate and extent of ALA recovery as measured by the maximum ALA concentration in the lymph (Cmax = 14 mg/ml at 3 h in the emulsion group v. 9 mg/ml at 5 h in the oil group; P < 0·05). Likewise, the area under the curve of the kinetics was significantly higher in the emulsion group (48 mg × h/ml for rats fed emulsion v. 26 mg × h/ml for rats fed oil; P < 0·05). On the whole, ALA bioavailability was improved with flaxseed oil ingested in an emulsified state. Data obtained from the in vitro studies helped to partly interpret the physiological results.

Healing fats of the skin: the structural and immunologic roles of the omega-6 and omega-3 fatty acids.

Linoleic acid (18:2omega6) and alpha-linolenic acid (18:3omega3) represent the parent fats of the two main classes of polyunsaturated fatty acids: the omega-6 (n-6) and the omega-3 (n-3) fatty acids, respectively. Linoleic acid and alpha-linolenic acid both give rise to other long-chain fatty acid derivatives, including gamma-linolenic acid and arachidonic acid (omega-6 fatty acids) and docosahexaenoic acid and eicosapentaenoic acid (omega-3 fatty acids). These fatty acids are showing promise as safe adjunctive treatments for many skin disorders, including atopic dermatitis, psoriasis, acne vulgaris, systemic lupus erythematosus, nonmelanoma skin cancer, and melanoma. Their roles are diverse and include maintenance of the stratum corneum permeability barrier, maturation and differentiation of the stratum corneum, formation and secretion of lamellar bodies, inhibition of proinflammatory eicosanoids, elevation of the sunburn threshold, inhibition of proinflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, and interleukin-12), inhibition of lipoxygenase, promotion of wound healing, and promotion of apoptosis in malignant cells, including melanoma. They fulfill these functions independently and through the modulation of peroxisome proliferator-activated receptors and Toll-like receptors.

Trans-membrane uptake and intracellular metabolism of fatty acids in Atlantic salmon (Salmo salar L.) hepatocytes.

To elucidate if the trans-membrane uptake of fatty acids is protein-mediated, the uptake of oleic acid (18:1n-9), linoleic acid (18:2n-6), alpha-linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) was investigated in vitro in Atlantic salmon (Salmo salar L.) primary hepatocytes. Firstly, optimal fatty acid incubation time and concentration were established for trans-membrane 18:n-9 uptake. Based on saturation kinetics, a 2-h incubation time and 37.5 muM were used for the following experiments. Secondly, in order to identify whether trans-membrane fatty acid uptake in hepatocytes was mainly passive or protein mediated, hepatocytes were pre-incubated with membrane protein inhibitors followed by 2 h of incubation with [1-(14)C] labelled 18:1n-9, 18:2n-6, 18:3n-3, 20:5n-3 and 22:6n-3. Fatty acid uptake into hepatocytes was highest with 20:5n-3 and 22:6n-3 and lowest with 18:1n-9. Phloretin was the most potent fatty acid uptake inhibitor, inhibiting uptake in the following order: 20:5n-3 > 18:3n-3 = 22:6n-3 > 18:2n-6 > 18:1n-9. The uptake of FA in Atlantic salmon hepatocytes seem to be due to both saturable and inhibitable protein mediated uptake, as well as passive uptake processes with more unsaturated and long fatty acids (20:n-3 > 22:6n-3 = 18:3n-3 > 18:2n-6) being more dependent on membrane protein mediated uptake compared to 18:1n-9.

Distribution of omega-3 fatty acids in tissues of rabbits fed a flaxseed-supplemented diet.

Diets rich in omega-3 polyunsaturated fatty acids are associated with decreased incidences of cardiovascular disease. The extent of incorporation and distribution of these beneficial fats into body tissues is uncertain. Rabbits were fed regular rabbit chow or a diet containing 10% ground flaxseed that is highly enriched with the omega-3 polyunsaturated fatty acid alpha-linolenic acid (ALA). The high-flaxseed diet resulted in an incorporation of ALA in all tissues, but mostly in the heart and liver with little in the brain. Docosahexaenoic and eicosapentaenoic acid levels were also selectively increased in some tissues, and the effects were not as large as ALA. Arachidonic acid and the ratio of omega-6/omega-3 fatty acids were decreased in all tissues obtained from the flax-supplemented group. Consumption of dietary flaxseed appears to be an effective means to increase ALA content in body tissues, but the degree will depend upon the tissues examined.

Alpha-linolenic acid and its conversion to longer chain n-3 fatty acids: benefits for human health and a role in maintaining tissue n-3 fatty acid levels.

There is little doubt regarding the essential nature of alpha-linolenic acid (ALA), yet the capacity of dietary ALA to maintain adequate tissue levels of long chain n-3 fatty acids remains quite controversial. This simple point remains highly debated despite evidence that removal of dietary ALA promotes n-3 fatty acid inadequacy, including that of docosahexaenoic acid (DHA), and that many experiments demonstrate that dietary inclusion of ALA raises n-3 tissue fatty acid content, including DHA. Herein we propose, based upon our previous work and that of others, that ALA is elongated and desaturated in a tissue-dependent manner. One important concept is to recognize that ALA, like many other fatty acids, rapidly undergoes beta-oxidation and that the carbons are conserved and reused for synthesis of other products including cholesterol and fatty acids. This process and the differences between utilization of dietary DHA or liver-derived DHA as compared to ALA have led to the dogma that ALA is not a useful fatty acid for maintaining tissue long chain n-3 fatty acids, including DHA. Herein, we propose that indeed dietary ALA is a crucial dietary source of n-3 fatty acids and its dietary inclusion is critical for maintaining tissue long chain n-3 levels.