Ω3 Polyunsaturated Fatty Acids Research Articles

Fish Oil Inhibits Human Lung Carcinoma Cell Growth by Suppressing Integrin-Linked Kinase

We previously showed that synthetic peroxisome proliferator-activated receptor gamma (PPARgamma) ligands inhibit non-small cell lung carcinoma (NSCLC) cell growth through multiple signaling pathways. Here, we show that dietary compounds, such as fish oil (which contains certain kinds of fatty acids like omega3 and omega6 polyunsaturated fatty acids), also inhibit NSCLC cell growth by affecting PPARgamma and by inhibiting the expression of integrin-linked kinase (ILK). Exogenous expression of ILK overcame, whereas silencing ILK enhanced the inhibitory effect of fish oil on cell growth. The inhibitor of p38 mitogen-activated protein kinase, SB239023, abrogated the inhibitory effect of fish oil on ILK expression, whereas the inhibitor of extracellular signal-regulated kinase, PD98059, had no effect. Transient transfection experiments showed that fish oil reduced ILK promoter activity, and this effect was abolished by AP-2alpha small interfering RNA and SB239023 and by deletion of a specific portion of the ILK gene promoter. Western blot analysis and gel mobility shift assay showed that fish oil significantly induced AP-2alpha protein expression and AP-2 DNA-binding activity in the ILK gene promoter and that this was dependent on PPARgamma activation. Blockade of AP-2alpha abrogated the effect of fish oil on ILK expression and on cell growth, whereas exogenous expression of AP-2alpha enhanced cell growth in the setting of fish oil exposure. Taken together, these findings show that fish oil inhibits ILK expression through activation of PPARgamma-mediated and p38 mitogen-activated protein kinase-mediated induction of AP-2alpha. In turn, this leads to inhibition of NSCLC cell proliferation. This study unveils a novel mechanism by which fish oil inhibits human lung cancer cell growth.

Nutrition for the Eye: Different Susceptibility of the Retina and the Lacrimal Gland to Dietary Omega-6 and Omega-3 Polyunsaturated Fatty Acid Incorporation

The purpose of this study was to compare the susceptibility of the retina and the exorbital lacrimal gland to dietary supplies of long-chain omega-3 (ω3) and omega-6 (ω6) polyunsaturated fatty acids (LC-PUFAs). Male Wistar rats were fed a 5% lipid diet containing: (1) 10% eicosapentaenoic acid (EPA) and 7% docosahexaenoic acid (DHA), or (2) 10% γ-linolenic acid (GLA), or (3) 10% EPA, 7% DHA and 10% GLA or (4) a balanced diet deprived of EPA, DHA and GLA for 3 months. Lipids were extracted from plasma phospholipids, retina and exorbital lacrimal gland, and fatty acid composition was determined by gas chromatography. Dietary supplementation with EPA and DHA increased ω3 PUFA levels in plasma phospholipids as well as in the retina and the exorbital lacrimal gland. By contrast, GLA supplementation favored ω6 PUFA incorporation, and particularly the incorporation of the end-chain ω6 product, docosapentaenoic acid (DPA), into all tissues. Supplementation with EPA, DHA and GLA increased the levels of DHA, EPA and dihomo-GLA (dGLA), whereas arachidonic acid (AA) was unchanged and DPA decreased in the retina and the lacrimal gland. The ability of both tissues to incorporate PUFAs from blood was evaluated. The results showed that the retina was more selective than the lacrimal gland for EPA. In spite of the different susceptibility of the retina and the lacrimal gland to dietary PUFAs, these results suggest that the concomitant use of dietary ω3 and ω6 PUFAs may be useful in modulating inflammation in both tissues.

Seasonal variations in lipid composition of the hydrothermal vent mussel Bathymodiolus azoricus from the Menez Gwen vent field

Specimens of the hydrothermal mussel Bathymodiolus azoricus collected in Menez Gwen hydrothermal vent field (NE Atlantic) during 2002–2003 were examined for feeding patterns variations through three seasons. The fatty acid profile and lipid classes of the mussels were studied, together with the MODIS/AQUA-derived near-surface chlorophyll a to test the hypothesis that surface productivity might be related to the feeding patterns of this species. The lipid levels showed pronounced seasonal fluctuations with the highest values occurring in January and August. Seasonal variations in lipid classes and fatty acid composition of neutral and polar lipids in the mussels are presented. Differences in the fatty acid profile of lipid classes in different seasons suggest that the higher energy requirements in summer and winter were supplied by bacterial biomarkers ω7 MUFA (monounsaturated fatty acids), whereas ω6 PUFA (polyunsaturated fatty acids) and NMI (non-methylene-interrupted) fatty acids predominated during the spring. The MODIS/AQUA data show marked seasonal variability and an anomalous peak during January of 2003, although this cannot be directly linked to lipid composition variation.

Avaliação bromatológica e perfil de ácidos graxos da carne de frangos de corte alimentados com rações contendo farinha de peixe ou aveia-branca

Objetivou-se analisar a composição química e o perfil de ácidos graxos (AG) da carne de frangos (peito e coxa/sobrecoxa) alimentados com rações contendo farinha de peixe e aveia. O delineamento experimental foi inteiramente casualizado, com cinco tratamentos, três repetições e dez aves por unidade experimental. Como tratamentos, avaliaram-se rações contendo: 4,5 ou 9% de farinha de peixe; 10 ou 20% de aveia; e ração-testemunha. Não houve diferença significativa na composição química do peito. As amostras de coxa/sobrecoxa das aves alimentadas com dietas formuladas com 9% de farinha de peixe e 10% de aveia apresentaram maior quantidade de lipídios em comparação às obtidas com as rações controle e com 20% de aveia. A composição de ácidos graxos saturados, tanto do peito como da coxa/sobrecoxa, não diferiu entre as aves. A ração com 20% de aveia aumentou a quantidade de ácido palmitoléico no peito em comparação àquela com 9% de farinha de peixe. O acúmulo deste ácido graxo nas amostras de coxa/sobrecoxa foi maior nas aves alimentadas com as rações contendo aveia e menor naquelas alimentadas com 9% de farinha de peixe. Em comparação às rações com aveia, a ração com 9% de farinha de peixe apresentou maior potencial de aumento dos ácidos graxos poliinsaturados ω-3 (α-linolênico) no peito e ω-6 na coxa/sobrecoxa. Entretanto, a ração contendo 9% de farinha de peixe ocasionou maior acúmulo de ω-3 na coxa/sobrecoxa. A utilização de aveia na ração melhora o perfil de ácidos graxos monoinsaturados, especialmente o palmitoléico, enquanto a utilização de 9% de farinha de peixe na ração melhora o perfil dos ácidos graxos poliinsaturados, principalmente ω-6 e ω-3.

Letter by Pignier and Le Grand Regarding Article “Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure”

HomeCirculationVol. 118, No. 3Letter by Pignier and Le Grand Regarding Article “Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Pignier and Le Grand Regarding Article “Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure” Christophe Pignier, PhD and Bruno Le Grand, PhD Christophe PignierChristophe Pignier Pierre Fabre Research Center, Cardiovascular Diseases II Division, Castres, France Search for more papers by this author and Bruno Le GrandBruno Le Grand Pierre Fabre Research Center, Cardiovascular Diseases II Division, Castres, France Search for more papers by this author Originally published15 Jul 2008https://doi.org/10.1161/CIRCULATIONAHA.108.778373Circulation. 2008;118:e69To the Editor:We read with a great interest the article by den Ruijter et al,1 which showed that acute application of ω3-polyunsaturated fatty acids (DHA and EPA) reduced action potential duration and decreased diastolic and systolic intracellular calcium in myocytes from pathological hearts explanted from rabbits and humans. Consequently, ω3-polyunsaturated fatty acids abolished triggered activity and reduced the number of delayed afterdepolarizations and calcium levels after transients.The purpose of our letter is to point out that a major mechanism is missing from those proposed by the authors: inhibition by ω3-polyunsaturated fatty acids of the persistent sodium current. In contrast to the well-known rapid sodium channels that activate and inactivate very quickly, a different mode of gating has been reported. Channels that fail to inactivate completely produce a late or persistent sodium current that is responsible for a long-lasting influx of Na+, which is converted in Ca2+ overload through the activation of the reverse mode of the Na+–Ca2+ exchanger. Persistent sodium current (INa) amplitude is increased in patients with an history of cardiac ischemia2 and in some patients with mutations in the SCN5A gene. Therefore, enhancement of persistent INa is observed and is associated with cellular damages and left ventricular dysfunction in a variety of pathological states, including heart failure.3,4 It has now become apparent that persistent INa plays an important role in the genesis of ischemia-induced ventricular damages and also in arrhythmias observed in failing hearts and that persistent INa represents an attractive target to focus on to provide protection from Na+-induced Ca2+ overload. We previously reported5 that DHA and EPA, in a same range of concentration used in the study by den Ruijter et al,1 concentration-dependently reduced the persistent INa artificially induced with veratridine, as well as the one involved in LQT3 syndrome.We do not claim that inhibition of persistent INa by ω3-polyunsaturated fatty acids is the unique mechanism to prevent triggered activity in myocytes, but we strongly believe that this effect constitutes a key mechanism for the reduction of the abnormalities of calcium homeostasis in failing heart.DisclosuresNone. References 1 den Ruijter HM, Berecki G, Verkerk AO, Bakker D, Baartscheer A, Schumacher CA, Belterman CNW, de Jonge N, Fiolet JWT, Brower IA, Coronel R. Acute administration of fish oil inhibits triggered activity in isolated myocytes from rabbits and patients with heart failure. Circulation. 2008; 117: 536–544.LinkGoogle Scholar2 Saint DA. The role of the persistent Na+ current during cardiac ischemia and hypoxia. J Cardiovasc Electrophysiol. 2006; 17: S96–S103.CrossrefMedlineGoogle Scholar3 Undrovinas AI, Maltsev VA, Sabbath HN. Repolarization abnormalities in cardiomyocytes of dogs with chronic heart failure: role of sustained inward current. Cell Mol Life Sci. 1999; 55: 494–505.CrossrefMedlineGoogle Scholar4 Valdivia CR, Chu WW, Pu J, Foell JD, Haworth RA, Wolff MR, Kamp TJ, Makielski JC. Increased late sodium current in myocytes from a canine heart failure model and from failing human heart. J Mol Cell Cardiol. 2005; 38: 475–483.CrossrefMedlineGoogle Scholar5 Pignier C, Revenaz C, Rauly-Lestienne I, Cussac D, Delhon A, Gardette J, Le Grand B. Direct protective effects of poly-unsaturated fatty acids, DHA and EPA, against activation of cardiac late sodium current: a mechanism for ischemia selectivity. Basic Res Cardiol. 2007; 102: 553–564.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 15, 2008Vol 118, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.108.778373PMID: 18625900 Originally publishedJuly 15, 2008 PDF download Advertisement SubjectsArrhythmias

Response to Letter Regarding Article “Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure”

We thank Drs Pignier and LeGrand for their interest in our work.1 In their letter, Drs Pignier and LeGrand express their belief that inhibition of the persistent component of the sodium current (INa,P) constitutes a key mechanism of the antiarrhythmic properties of ω3-polyunsaturated fatty acids in heart failure in our study,1 a …

Significance of omega-3 polyunsaturated fatty acid administration in the therapeutic approach of depression in hemodialysis patients

According to various reports and clinical studies mentaldisorders represent a frequent sequela of chronic diseases.In end stage renal disease, in particular, mood disordersand more specifically major depression is met with a fre-quency of 20-30% and is the most widely acknowledgedabnormality [1]. As a consequence, overall quality of lifeas well as treatment compliance is severely impaired [2].Omega-3 (Ω3) polyunsaturated fatty acids (PUFAs) havebeen shown to reduce the risk and to treat mental disor-ders including depression [3]. However, evidence to date,remains obscure and recommendations must be givenwith caution [4]. The aim of the present study was to eval-uate the significance of Ω3 administration in the treat-ment of depressive maintenance hemodialysis (HD)patients.

Human Neutrophils Convert the Sebum-derived Polyunsaturated Fatty Acid Sebaleic Acid to a Potent Granulocyte Chemoattractant

Sebaleic acid (5,8-octadecadienoic acid) is the major polyunsaturated fatty acid in human sebum and skin surface lipids. The objective of the present study was to investigate the metabolism of this fatty acid by human neutrophils and to determine whether its metabolites are biologically active. Neutrophils converted sebaleic acid to four major products, which were identified by their chromatographic properties, UV absorbance, and mass spectra as 5-hydroxy-(6E,8Z)-octadecadienoic acid (5-HODE), 5-oxo-(6E,8Z)-octadecadienoic acid (5-oxo-ODE), 5S,18-dihydroxy-(6E,8Z)-octadecadienoic acid, and 5-oxo-18-hydroxy-(6E,8Z)-octadecadienoic acid. The identities of these metabolites were confirmed by comparison of their properties with those of authentic chemically synthesized standards. Both neutrophils and human keratinocytes converted 5-HODE to 5-oxo-ODE. This reaction was stimulated in neutrophils by phorbol myristate acetate and in keratinocytes by oxidative stress (t-butyl-hydroperoxide). Both treatments dramatically elevated intracellular levels of NADP(+), the cofactor required by 5-hydroxyeicosanoid dehydrogenase. In keratinocytes, this was accompanied by a rapid increase in intracellular GSSG levels, consistent with the involvement of glutathione peroxidase. 5-Oxo-ODE stimulated calcium mobilization in human neutrophils and induced desensitization to 5-oxo-6,8,11,14-eicosatetraenoic acid but not leukotriene B(4), indicating that this effect was mediated by the OXE receptor. 5-Oxo-ODE and its 8-trans isomer were equipotent with 5-oxo-6,8,11,14-eicosatetraenoic acid in stimulating actin polymerization and chemotaxis in human neutrophils, whereas 5-HODE, 5-oxo-18-hydroxy-(6E,8Z)-octadecadienoic acid, and 5S,18-dihydroxy-(6E,8Z)-octadecadienoic acid were much less active. We conclude that neutrophil 5-lipoxygenase converts sebaleic acid to 5-HODE, which can be further metabolized to 5-oxo-ODE by 5-hydroxyeicosanoid dehydrogenase in neutrophils and keratinocytes. Because of its chemoattractant properties, sebum-derived 5-oxo-ODE could be involved in neutrophil infiltration in inflammatory skin diseases.

Cyclic GMP/Protein Kinase G Phosphorylation of Smad3 Blocks Transforming Growth Factor-β–Induced Nuclear Smad Translocation

See related article, pages 185–192 In response to hemodynamic overload, the heart undergoes a complex adaptive remodeling process that involves cardiac myocyte hypertrophy, transformation of fibroblast into myofibroblast, high-level expression of extracellular matrix (ECM) proteins, interstitial fibrosis, and cell death.1 Differentiation of cardiac fibroblasts into myofibroblasts is critical to the production and deposition of collagens and plays a decisive role in myocardial fibrosis and morphological alterations during the progression of adaptive myocardial hypertrophy to decompensation and heart failure.1,2 Among the plethora of identified fibrogenic factors, transforming growth factor (TGF)-β3 plays a fundamental role in hypertrophic and fibrotic remodeling of the heart, where it regulates cardiomyocyte growth, fibroblast activation, and ECM deposition.4,5 The expression of ventricular TGF-β mRNA and protein is increased in numerous models of pathological cardiac hypertrophy and in cardiac cells in response to putative hypertrophic stimuli.6,7 In vitro, TGF-β activates myofibroblast transformation and increases ECM production.7 Blockade of TGF-β signaling is predicted to blunt fibrosis.5 Recent studies from Chen et al8 convincingly demonstrated that disruption of TGF-β signaling by inducible dominant-negative mutation of the TGF-β receptor type II (TβRII) gene significantly reduced the pressure overload–induced myofibroblast transformation and interstitial fibrosis in mouse heart. Thus, there is considerable interest in understanding how signaling by TGF-β receptors is transduced and how the inevitable damage produced could be mitigated. Of the 3 isoforms of TGF-β expressed in mammals,9,10 TGF-β1 is expressed in the adult heart, where it is secreted by cardiomyocytes and myofibroblasts and retained in significant amounts in ECM as a latent cytokine. Recent advances have led to clear description of downstream of TGF-β signal transduction pathways initiated by binding of TGF-β to membrane-bound heteromeric receptor kinases (TβRI and TβRII) that transduce intracellular signals via both Smad and non-Smad pathways …

Use of differently enriched rotifers,Brachionus plicatilis, during larviculture of haddock,Melanogrammus aeglefinus: effects on early growth, survival and body lipid composition

We evaluated the effects of enriched rotifers on growth, survival and on the lipid composition of haddock larvae. The treatments tested were (1) AlgaMac 2000®, (2) AquaGrow® Advantage and (3) Pavlova sp. paste and AlgaMac 2000®. The treatments did not influence larval growth rate throughout the experimental period (P = 0.70). Larvae from all treatments grew approximately 8% of their dry weight per day between 1 and 29 days post hatch (dph). Treatment 3 resulted in the best survival, estimated to be 3 on a scale from 0 to 5, whereas for the two other groups the survival estimates were 0 and 2. Rotifers from treatment 1 had low sterol concentrations, high eicosapentaenoic acid/arachidonic acid ratio and their feeding resulted in high larval mortality. Rotifers enriched with Pavlova sp. had the lowest proportions of the sum of saturated fatty acids, docosahexaenoic acid and sum of ω3 and the highest proportions of the sum of monounsaturated fatty acids (ΣMUFA). This was partially reflected in larvae from treatment 3 in that they had the highest proportions of ΣMUFA and the lowest proportions of Σω3 (P < 0.0001 for both analyses). In addition, these larvae had the highest and lowest ΣC20 and ΣC22 polyunsaturated fatty acids (PUFA) respectively (P < 0.0001 for both analyses). We suggest that more research with ω3 and ω6 PUFA can lead to improvements in the rearing of haddock larvae produced in hatcheries.

Cyclooxygenase-2–Derived Prostaglandin E2 Activates β-Catenin in Human Cholangiocarcinoma Cells: Evidence for Inhibition of These Signaling Pathways by ω3 Polyunsaturated Fatty Acids

Cholangiocarcinoma is a highly malignant neoplasm of the biliary tree. It has a high rate of mortality, and currently, there is no effective chemoprevention and treatment. This study was designed to investigate the potential effect of omega 3 polyunsaturated fatty acids (omega 3-PUFA) on human cholangiocarcinoma cell growth and to determine their mechanisms of actions. Treatment of three human cholangiocarcinoma cells (CCLP1, HuCCT1, SG231) with two omega 3-PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), for 12 to 72 h resulted in a dose- and time-dependent inhibition of cell growth; in contrast, arachidonic acid, a omega 6-PUFA, had no significant effect. The omega 3-PUFA effect is due to the induction of apoptosis, given that DHA induced the cleaved form of PARP, caspase-3, and caspase-9. DHA and EPA treatment caused dephosphorylation (and hence, the activation) of glycogen synthase kinase-3beta (GSK-3beta) with a decline of beta-catenin protein. Accordingly, DHA treatment also decreased the beta-catenin-mediated T cell factor/lymphoid enhancer factor (TCF/LEF) reporter activity, and inhibited the expression of c-Met, a beta-catenin-controlled downstream gene implicated in cholangiocarcinogenesis. The GSK-3beta inhibitor, SB216763, partially prevented DHA-induced reduction of beta-catenin protein and TCF/LEF reporter activity, and restored cell growth, suggesting the involvement of GSK-3beta dephosphorylation in omega 3-PUFA-induced beta-catenin degradation. In parallel, DHA treatment also induced the formation of the beta-catenin/Axin/GSK-3beta binding complex, further leading to beta-catenin degradation. Moreover, DHA inhibited the expression of cyclooxygenase-2 (COX-2) and enhanced the expression of 15-hydroxyprostaglandin dehydrogenase, a physiologic COX-2 antagonist, in human cholangiocarcinoma cells. These findings suggest that omega 3-PUFAs block cholangiocarcinoma cell growth at least in part through inhibition of Wnt/beta-catenin and COX-2 signaling pathways. Thus, utilization of omega 3-PUFAs may represent an effective and safe therapeutic approach for the chemoprevention and treatment of human cholangiocarcinoma.

Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure

Fish oil reduces sudden death in patients with prior myocardial infarction. Sudden death in heart failure may be due to triggered activity based on disturbed calcium handling. We hypothesized that superfusion with omega3-polyunsaturated fatty acids (omega3-PUFAs) from fish inhibits triggered activity in heart failure. Ventricular myocytes were isolated from explanted hearts of rabbits with volume- and pressure-overload-induced heart failure and of patients with end-stage heart failure. Membrane potentials (patch-clamp technique) and intracellular calcium (indo-1 fluorescence) were recorded after 5 minutes of superfusion with Tyrode's solution (control), omega-9 monounsaturated fatty acid oleic acid (20 micromol/L), or omega3-PUFAs (docosahexaenoic acid or eicosapentaenoic acid 20 micromol/L). omega3-PUFAs shortened the action potential at low stimulation frequencies and caused an approximately 25% decrease in diastolic and systolic calcium (all P<0.05). Subsequently, noradrenalin and rapid pacing were used to evoke triggered activity, delayed afterdepolarizations, and calcium aftertransients. omega3-PUFAs abolished triggered activity and reduced the number of delayed afterdepolarizations and calcium aftertransients compared with control and oleic acid. Omega3-PUFAs reduced action potential shortening and intracellular calcium elevation in response to noradrenalin. Results from human myocytes were in accordance with the findings obtained in rabbit myocytes. Superfusion with omega3-PUFAs from fish inhibits triggered arrhythmias in myocytes from rabbits and patients with heart failure by lowering intracellular calcium and reducing the response to noradrenalin.

L‐glutamine and palmitate catabolism in pancreatic islets from rats depleted in long‐chain polyunsaturated ω3 fatty acids

The catabolism of D-glucose was recently found to be impaired in pancreatic islets from rats depleted in long-chain polyunsaturated omega3 fatty acids. The specificity of this alteration was now investigated by characterizing the oxidative fate of endogenous nutrients in islets preincubated with either L-[U-14C]glutamine or [U-14C]palmitate and then incubated variously in the absence of D-glucose, presence of the hexose or presence of metabolic poisons. Relative to their radioactive content after preincubation, the production of 14CO2 by islets prelabelled with [U-14C]glutamine was higher in omega3-depleted rats than control animals. The enhancing action of D-glucose upon such production was impaired, however, in the omega3-depleted rats. The net uptake of 14C-palmitate and absolute value for 14CO2 output were both increased in omega3-depleted rats, whilst the ratio between 14CO2 output and islet radioactive content was decreased in the same animals. The inhibition of 14CO2 production by metabolic poisons was comparable in all cases. These results are consistent with recent findings on such items as the availability of endogenous amino acids and uptake of unesterified fatty acids in extrapancreatic sites of the omega3-depleted rats. They also support the view that the alteration of D-glucose metabolism in the islets of the latter animals may be attributable, in part at least, to alteration of glucokinase kinetics by high intracellular acyl-CoA levels.

Long‐chain fatty acyl‐coenzyme A‐induced inhibition of glucokinase in pancreatic islets from rats depleted in long‐chain polyunsaturated ω3 fatty acids

The metabolism of D-glucose was recently reported to be impaired in pancreatic islets from second generation rats depleted in long-chain polyunsaturated omega3 fatty acids. Considering the increased clearance of circulating non-esterified fatty acids prevailing in these rats, a possible inhibition of glucokinase in insulin-producing cells by endogenous long-chain fatty acyl-CoA was considered. The present study was mainly aimed at assessing the validity of the latter proposal. The activity of glucokinase in islet homogenates, as judged from the increase in D-glucose phosphorylation rate in response to a rise in the concentration of the hexose represented, in the omega3-depleted rats, was only 81.8 +/- 4.8% (n = 11; p < 0.005) of the paired value recorded in control animals. This coincided with the fact that the inclusion of D-glucose 6-phosphate (3.0 mM) and D-fructose 1-phosphate (1.0 mM) in the assay medium resulted in a lesser fractional decrease of D-glucose phosphorylation in omega3-depleted rats than in control animals. Moreover, whereas palmitoyl-CoA (50 microM) decreased the activity of glucokinase by 38.0 +/- 6.0% (n = 4; p < 0.01) in islet homogenates from normal rats, the CoA ester failed to affect significantly the activity of glucokinase in islet homogenates from omega3-depleted rats. These findings afford direct support for the view that glucokinase is indeed inhibited by endogenous long-chain fatty acyl-CoA in islets from omega3-depleted rats, such an inhibition probably participating to the alteration of D-glucose catabolism prevailing in these islets.

Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements

There is considerable interest in the potential impact of several polyunsaturated fatty acids (PUFAs) in mitigating the significant morbidity and mortality caused by degenerative diseases of the cardiovascular system and brain. Despite this interest, confusion surrounds the extent of conversion in humans of the parent PUFA, linoleic acid or alpha-linolenic acid (ALA), to their respective long-chain PUFA products. As a result, there is uncertainty about the potential benefits of ALA versus eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Some of the confusion arises because although mammals have the necessary enzymes to make the long-chain PUFA from the parent PUFA, in vivo studies in humans show that asymptotically equal to 5% of ALA is converted to EPA and <0.5% of ALA is converted to DHA. Because the capacity of this pathway is very low in healthy, nonvegetarian humans, even large amounts of dietary ALA have a negligible effect on plasma DHA, an effect paralleled in the omega6 PUFA by a negligible effect of dietary linoleic acid on plasma arachidonic acid. Despite this inefficient conversion, there are potential roles in human health for ALA and EPA that could be independent of their metabolism to DHA through the desaturation - chain elongation pathway.

Développement du tissu adipeux : importance des lipides alimentaires

A well-balanced development of white adipose tissue (WAT) is physiologically important. Longitudinal studies indicate that excess of adipose tissue at early age is predictive of subsequent overweight and obesity, emphasizing infancy as a critical period for WAT development. In this respect, in response to a positive energy balance, its expansion takes place from adipocyte precursor cells which remain present throughout life. Moreover, lipoatrophy and lipodystrophy on one hand, overweight and obesity on the other hand, lead to the metabolic syndrome. In obese patients, the earlier is the obesity onset, the higher is adipocyte size and even more so adipocyte number. As adipocytes do not divide, this observation indicates that excessive proliferation of adipocyte precursor cells is a critical issue, hampered by the lack of specific markers of these cells which represent the true potential of WAT development. In animals and humans, both cross-sectional and longitudinal studies have shown that a caloric excess, i.e. fat-enriched foods in most cases, is associated to enhanced fat mass. The role of dietary fat as a major player in adult human obesity remains controversial because the prevalence of overweight and obesity has increased dramatically over the last decades despite no recent major change in the amount of ingested fats. However the importance of qualitative changes in the fatty acid composition of fats has been largely disregarded despite a dramatic alteration over decades of the balance of essential polyunsaturated fatty acids (PUFAs). There is evidence from animal and human studies that changes in the balance of ω6 and ω3 PUFAs may alter the early stages of adipose tissue development. Under isonenergetic conditions, pups from wild-type mother mice fed a linoleic acid (LA)-enriched diet were 40% heavier 1 week after weaning than those from mothers fed a LA/α-linolinenic acid (LA/LNA) diet, and the weight difference is maintained at the adult age. The LA-induced enhancement of fat mass is abolished in mice invalidated for the cell surface prostacyclin receptor (ip -/- mice), demonstrating the critical role of arachidonic acid and prostacyclin in excessive adipose tissue development. Changes observed in the past decades in the fatty acid composition of dietary fats observed in breast milk and formula milk, i.e. an increase in LA with slight or no change in LNA content, acting in concert with a positive energy balance, may be responsible at least in part for the dramatic rise in the prevalence of childhood overweight and obesity. The significant change in the composition of PUFAs in most consumed foods can be traced to changes in human food habits but, quite importantly, also in the feeding pattern of breeding stock. Since prevention of obesity appears critical to avoid difficult if not insurmountable health problems in the future, and in addition to a better control of energy balance, the composition of dietary lipids should be reconsidered from the very beginning of the food chain.

Differentiation of the effects of arginine and w3 polyunsaturated fatty acids in an immune‐enhancing diet (IED).

Introduction: It has been shown that arginine (ARG) is more efficient in traumatized rats when added to a standard diet (Sondalis® HP(S)) than when included in an IED (Crucial® (C)). This could be due to high amounts of ω3 polyunsaturated fatty acids (PUFA) counteracting the beneficial effects of ARG. We therefore evaluated diets with different ARG and PUFA contents in a rat model of turpentine (T)-induced inflammation. Materials and methods: 42 SD rats were randomized into one of 5 groups: AL (ad libitum), TS, TC, TSA (S with ARG equimolar to the ARG in C), TMC (modified C with the same ω6/ω3 ratio as S). Rats received 290 kcal/kg/d and 3.29 g N/kg/d continuously from D0 to D4. T was injected subcutaneously (0.5 mL/100 g body weight) at D1 and D3. Following parameters were evaluated at D4: thymus weight, CD25 receptors density on blood lymphocytes, and bacterial translocation. Results and discussion: Table 1. Data are expressed as means ± SEM and were analyzed by ANOVA + Duncan's test; a ≠ b ≠ c at p<0.05. ARG also limited the number of bacteria in mesenteric lymph nodes. However, the effect of ARG was not reproduced with the IED (C or TMC). Conclusion: The beneficial effects of ARG included in an IED are not antagonized by ω3-PUFA.

Interactions between food quantity and quality (long-chain polyunsaturated fatty acid concentrations) effects on growth and development ofChironomus riparius

We quantified somatic growth, development, and emergence of the midge Chironomus riparius on experimental diets (oats, Spirulina, and Tetraphyll®) covering gradients in food quality (differing polyunsaturated fatty acids) and quantity (0.1–5.4 mg C·day–1). Additionally, similar incubations without food additions were made using a food-poor sediment containing peat and the green alga Scenedesmus obliquus. Larval and adult size was affected by both food quantity and quality and increased some three to four times across the food concentration gradients. Adult emergence, however, was affected only by food quantity. A type 3 response model showed that a saturation level was reached for the oats treatment at 2.7 mg C·day–1(or 3.9 µg ω3 and 120 µg ω6 polyunsaturated fatty acids·day–1), indicating that the quality of oats constrained further stimulation of larval growth. In the peat treatment, larval growth was very low, no adults emerged, and no larvae even made it to the pupa stage. Fatty acid analyses showed that larvae were capable of synthesizing arachidonic acid via γ-linolenic acid by Δ6- and Δ5-desaturase activity using linoleic acid available in food sources. This strongly suggests that C. riparius is not dependent on dietary sources of eicosapentaenoic acid and arachidonic acid and can sustain viable populations even under a low-quality food regimen.

Consumption of ω3-fatty acids during perinatal life: role in immuno-modulation and allergy prevention

Epidemiological data suggest that dietary factors may have a role in recent increases of the prevalence of allergic diseases. One food-related component might be the reduced consumption of omega3-polyunsaturated fatty acids observed especially in the Western societies; yet, clinical trials supplementing omega3-fatty acids to adults with established allergies and bronchial asthma have generally been disappointing. However, it is known that the immature immune system is highly susceptible to immuno-modulatory environmental conditions particularly in the pre- and postnatal period. This review discusses the immuno-modulatory effects of omega3-fatty acids supplementation in the perinatal life phase on the immune system of the child. Evidence exists that perinatal omega3-fatty acid exposure affects T-cells and antigen presenting cells of the neonates likely due to altered eicosanoid metabolism. Although animal experiments strongly suggest a role of maternal omega3-fatty acid intake on allergic immune responses in the offspring, the beneficial effect of omega3-fatty acid supplementation has been studied in a small number of clinical trials. In these studies perinatal supplementation had some positive effects on distinct clinical phenotypes of the atopic syndrome. However, more studies are needed to fully explore the opportunity of perinatal immuno-modulation.

1α,25-Dihydroxyvitamin D and fish oil synergistically inhibit G1/S-phase transition in prostate cancer cells

Laboratory and epidemiological studies have indicated that 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and dietary ω3-polyunsaturated fatty acids (PUFAs) are capable of inhibiting prostate cancer at the initiation and progression stages. The objective of this study is to investigate the influence of 1α,25(OH)2D3 and PUFAs in the form of fish oil applied alone or in combination on cell cycle kinetics in the exponentially growing androgen-dependent and -independent prostate cancer cells. Our data indicate that the high passage androgen-independent cell line, LNCaP-c115 had a much greater inhibitory response at the level of the G1/S-phase transition in response to fish oil treatment than androgen-dependent low passage LNCaP-c38 cells. When LNCaP-c38 and LNCaP-c115 cells were treated with fish oil (50μg/ml), 1α,25(OH)2D3 (10−8M) or fish oil (50μg/ml)+1α,25(OH)2D3 (10−8M), a synergistic growth inhibitory effect was observed with 1α,25(OH)2D3+fish oil group in LNCaP-c115 cell line at the levels of the G1/S-phase transition and cell division. This interaction appears to be specific for androgen-independent prostate cancer cell lines. Based on these results, we hypothesize that dietary components, such as ω3PUFAs and Vitamin D, have the potential to delay the progression of prostate cancer cells to an aggressive and un-treatable state.