Action Of Polyunsaturated Fatty Acids Research Articles

Unexpected omega-3 activities in intracellular lipolysis and macrophage foaming revealed by fluorescence lifetime imaging

Omega-3 polyunsaturated fatty acids (PUFA) found primarily in fish oil have been a popular supplement for cardiovascular health because they can substantially reduce circulating triglyceride levels in the bloodstream to prevent atherosclerosis. Beyond this established extracellular activity, here, we report a mode of action of PUFA, regulating intracellular triglyceride metabolism and lipid droplet (LD) dynamics. Real-time imaging of the subtle and highly dynamic changes of intracellular lipid metabolism was enabled by a fluorescence lifetime probe that addressed the limitations of intensity-based fluorescence quantifications. Surprisingly, we found that among omega-3 PUFA, only docosahexaenoic acid (DHA) promoted the lipolysis in LDs and reduced the overall fat content by approximately 50%, and consequently helped suppress macrophage differentiation into foam cells, one of the early steps responsible for atherosclerosis. Eicosapentaenoic acid, another omega-3 FA in fish oil, however, counteracted the beneficial effects of DHA on lipolysis promotion and cell foaming prevention. These in vitro findings warrant future validation in vivo.

Influence of pre-baking and frozen storage on the technological and nutritional quality of a multi-seed bread

Today's tendency is to prepare baking products by replacing wheat flour with wholemeal flours, and submitting them to preparation processes so they can be eaten at any time, to guarantee their nutritional and organoleptic properties, such as high-value nutritional food, and to extend the shelf life of the product, for more demanding consumers. This work's originality is shown in its holistic exploration of innovative baking practices, its unique approach regarding preservation through prebaking/freezing/storage, and its meticulous examination of nutritional and technofunctional attributes of an optimal formulation with innovative ingredients. This work studies the behaviour of easily made, multiseed bread made with quinoa, chia and amaranth flours to prepare and eat by applying a prebaking/freezing/storage process. The results were compared to the control product made only with wheat flour, which was processed under the same conditions. The technofunctional and nutritional properties (mineral bioavailability, amino acids content and fatty acids profile), and the prebaking-freezing effect on them, were investigated. Essential amino acids (EAAs; i.e., lysine, valine, leucine) were not lost during the frozen storage process, and respectively exceeded the control product by 50%, 10% and 5%. The difference in colour (ΔE*) between the control and the multiseed products was below 5 after baking/storage, which indicates that a colour change could not be perceived by consumers. After freezes storage, amylopectin retrogradation enthalpy was up to 33% lower than in the control sample, possibly due to the action of polyunsaturated fatty acids and the soluble fibre content present in the multiseed product. This bread formulation could meet adults' nutritional requirements regarding calcium and diet fibre with a daily intake of 100 g.

Polyunsaturated Fatty Acids (PUFAs): Sources, Digestion, Absorption, Application and Their Potential Adjunctive Effects on Visual Fatigue.

When the eyes are exposed to the environment, they are easily affected by strong light stimulation and harmful substances. At the same time, prolonged use of the eyes or incorrect eye habits can cause visual fatigue, which mainly manifests as eye dryness, soreness, blurred vision, and various discomforts. The main reason for this is a decline in the function of the eye, especially the cornea and retina on the surface of the eye, which have the greatest impact on the normal function of the eye. Research has found that supplementation with appropriate foods or nutrients can effectively strengthen the eye against external and internal stimuli, thereby alleviating or avoiding visual fatigue. Among these, supplementation with polyunsaturated fatty acids has been found to be effective at protecting eye health and relieving visual fatigue. This article summarizes the sources of polyunsaturated fatty acids (including the main dietary sources and internal synthesis), the mechanisms of digestion and absorption of polyunsaturated fatty acids in the body and the safety of polyunsaturated fatty acid applications. It also reviews the mechanism of action of polyunsaturated fatty acids in aiding the relief of visual fatigue based on the mechanism of impaired function or structure of the ocular surface and fundus in the hope of providing some reference and insight into the development and application of polyunsaturated fatty acids in functional foods for the relief of visual fatigue.

Polyunsaturated Fatty Acids: Conversion to Lipid Mediators, Roles in Inflammatory Diseases and Dietary Sources.

Polyunsaturated fatty acids (PUFAs) are important components of the diet of mammals. Their role was first established when the essential fatty acids (EFAs) linoleic acid and α-linolenic acid were discovered nearly a century ago. However, most of the biochemical and physiological actions of PUFAs rely on their conversion to 20C or 22C acids and subsequent metabolism to lipid mediators. As a generalisation, lipid mediators formed from n-6 PUFAs are pro-inflammatory while those from n-3 PUFAs are anti-inflammatory or neutral. Apart from the actions of the classic eicosanoids or docosanoids, many newly discovered compounds are described as Specialised Pro-resolving Mediators (SPMs) which have been proposed to have a role in resolving inflammatory conditions such as infections and preventing them from becoming chronic. In addition, a large group of molecules, termed isoprostanes, can be generated by free radical reactions and these too have powerful properties towards inflammation. The ultimate source of n-3 and n-6 PUFAs are photosynthetic organisms which contain Δ-12 and Δ-15 desaturases, which are almost exclusively absent from animals. Moreover, the EFAs consumed from plant food are in competition with each other for conversion to lipid mediators. Thus, the relative amounts of n-3 and n-6 PUFAs in the diet are important. Furthermore, the conversion of the EFAs to 20C and 22C PUFAs in mammals is rather poor. Thus, there has been much interest recently in the use of algae, many of which make substantial quantities of long-chain PUFAs or in manipulating oil crops to make such acids. This is especially important because fish oils, which are their main source in human diets, are becoming limited. In this review, the metabolic conversion of PUFAs into different lipid mediators is described. Then, the biological roles and molecular mechanisms of such mediators in inflammatory diseases are outlined. Finally, natural sources of PUFAs (including 20 or 22 carbon compounds) are detailed, as well as recent efforts to increase their production.

The role of omega-3 polyunsaturated fatty acids in the intensive care unit.

This review provides an update on the actions of omega-3 polyunsaturated fatty acids (PUFAs) and presents the most recent findings from trials in patients in the intensive care unit (ICU) setting including relevant meta-analyses. Many specialized pro-resolving mediators (SPMs) are produced from bioactive omega-3 PUFAs and may explain many of the beneficial effects of omega-3 PUFAs, although other mechanisms of action of omega-3 PUFAs are being uncovered. SPMs resolve inflammation, promote healing and support antiinfection activities of the immune system. Since publication of the ESPEN guidelines, numerous studies further support the use of omega-3 PUFAs. Recent meta-analyses favor the inclusion of omega-3 PUFAs in nutrition support of patients with acute respiratory distress syndrome or sepsis. Recent trials indicate that omega-3 PUFAs may protect against delirium and liver dysfunction in patients in the ICU, although effects on muscle loss are unclear and require further investigation. Critical illness may alter omega-3 PUFA turnover. There has been significant discussion about the potential for omega-3 PUFAs and SPMs in treatment of coronavirus disease 2019. Evidence for benefits of omega-3 PUFAs in the ICU setting has strengthened through new trials and meta-analyses. Nevertheless, better quality trials are still needed. SPMs may explain many of the benefits of omega-3 PUFAs.

Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system.

Omega-3 polyunsaturated fatty acids (PUFAs) can play important roles in maintaining mental health and resistance to stress, and omega-3 PUFAs supplementation can display beneficial effects on both the prevention and treatment of depressive disorders. Although the underlying mechanisms are still unclear, accumulated evidence indicates that omega-3 PUFAs can exhibit pleiotropic effects on the neural structure and function. Thus, they play fundamental roles in brain activities involved in the mood regulation. Since depressive symptoms have been assumed to be of central origin, this review aims to summarize the recently published studies to identify the potential neurobiological mechanisms underlying the anti-depressant effects of omega-3 PUFAs. These include that of (1) anti-neuroinflammatory; (2) hypothalamus-pituitary-adrenal (HPA) axis; (3) anti-oxidative stress; (4) anti-neurodegeneration; (5) neuroplasticity and synaptic plasticity; and (6) modulation of neurotransmitter systems. Despite many lines of evidence have hinted that these mechanisms may co-exist and work in concert to produce anti-depressive effects, the potentially multiple sites of action of omega-3 PUFAs need to be fully established. We also discussed the limitations of current studies and suggest future directions for preclinical and translational research in this field.

Polyunsaturated Fatty Acids as Prebiotics: Innovation or Confirmation?

The International Scientific Association for Probiotics and Prebiotics (ISAPP), in its last consensus statement about prebiotics, defined polyunsaturated fatty acids (PUFAs) as “candidate prebiotics” due to a lack of complete scientific evidence. Previous studies have demonstrated the ability of microbiota to metabolize PUFAs, although the role of the resulting metabolites in the host is less known. Recent partial evidence shows that these metabolites can have important health effects in the host, reinforcing the concept of the prebiotic action of PUFAs, despite the data being mostly related to omega-6 linoleic acid and to lactobacilli taxon. However, considering that the symbionts in our gut benefit from the nutritional molecules that we include in our diet, and that bacteria, like all living organisms, cannot benefit from a single nutritional molecule, the concept of the “correct prebiotic diet” should be the new frontier in the field of gut microbiota research.

Unsaturated fatty acid as functional food for the treatment of Diabetes mellitus type 2

Several studies have been demonstrating to a relationship between unsaturated fatty acids, improvement of pancreatic function and insulin secretion. In this context, this review presents the most recent findings on the pathophysiology of type 2 diabetes mellitus, the action mechanism of unsaturated fatty acids on pancreatic function, and clinical studies in diabetic patients. We evaluated here articles from MedLine/PubMed and the Science direct database, published between 2014 and 2020. Of the 637 results, 13 were selected. From their analysis, we could observe that mono and polyunsaturated fatty acids can improve glycemic control as well as reduce cardiovascular risk. The most recurrent antidiabetic action regarding monounsaturated fatty acids is the ability to preserve insulin signaling, whereas polyunsaturated fatty acids action consists in the increasing expression of the type 4 glucose transporter. However, a complete understanding of the relationship between fatty acids, insulin and inflammation should be considered in future investigations.

The central role of mitochondria in the relationship between dietary lipids and cancer progression.

Evidence demonstrates the importance of lipid metabolism and signaling in cancer cell biology. De novo lipogenesis is an important source of lipids for cancer cells, but exogenous lipid uptake remains essential for many cancer cells. Dietary lipids can modify lipids present in tumor microenvironment affecting cancer cell metabolism. Clinical trials have shown that diets rich in polyunsaturated fatty acids (PUFA) can negatively affect tumor growth. However, certain n-6 PUFAs can also contribute to cancer progression. Identifying the molecular mechanisms through which lipids affect cancer progression will provide an opportunity for focused dietary interventions that could translate into the development of personalized diets for cancer control. However, the effective mechanisms of action of PUFAs have not been fully clarified yet. Mitochondria controls ATP generation, redox homeostasis, metabolic signaling, apoptotic pathways and many aspects of autophagy, and it has been recognized to play a key role in cancer. The purpose of this review is to summarize the current evidence linking dietary lipids effects on mitochondrial aspects with consequences for cancer progression and the molecular mechanisms that underlie this association.

Cannabis seeds (Cannabis sativa L.) as a source of irreplaceable food components

The article presents the results of the analysis of literature sources that contain research data on the fatty acid composition of hemp oil (Cannabis sativa L.). Today, sown hemp is confidently occupying a segment of the food market, increasing the range. From ancient times the hemp was used as a source of fiber, from which woven garments were made, and the seeds were eaten. Later, nutritious oil was extracted from the seeds of the crop in the areas of hemp growing.
 In the twentieth century, researchers noticed to hemp oil and described in detail its fatty acid composition. The presence of polyunsaturated acids (ώ-3), in particular linolenic, in hemp oil puts the crop among the most valuable. A whole complex of other fatty acids was also found, such as palmitic, palmitoleic, stearic, oleic, linolenic, γ-linolenic, arachidonic, behenic, lignoceric, and others. According to various authors, modern varieties of hemp, both domestic and foreign selection, are characterized by different ratios of fatty acids in the oil, with unsaturated acids predominating. Linoleic, linolenic and arachidonic fatty acids (or vitamin F) prevent the deposition of cholesterol in the arteries, ensure healthy skin and hair, have a positive effect on the activity of the endocrine glands, help reduce body weight by burning saturated fats. These fatty acids are a source of formation in the body of biologically active substances ‒ prostaglandins. Especially valuable in hemp oil is the presence of linoleic, linolenic and gamma-linolenic acids. These important acids are found in large quantities in nature quite rarely. In the quantitative composition of the ratio of glycerides of these acids in hemp oil 3 : 1 (56 linoleic and 19 % linolenic). The most important physiological action of polyunsaturated fatty acids is a strong antisclerotic effect, the ability to lower blood cholesterol, reduce growth and even resorb atherosclerotic plaques. The use of α-linolenic acid prevents the oxidation of cell membrane lipids, insulin resistance, promotes normal fetal development, growth processes, proper development of the brain, visual organs, gonads, improves the biochemistry of the nervous system, synapses, nerve impulse transmission, brain blood pressure and blood cholesterol levels. The article also covers the agronomic characteristics of hemp fruit, as well as the peculiarities of lipid formation processes.

Antidepressant activity of \u03c9-3 polyunsaturated fatty acids in ovariectomized rats: role of neuroinflammation and microglial polarization

BackgroundMenopause predisposes individuals to affective disorders, such as depression, which is tightly related to neuroinflammation. While the neuroinflammatory condition has been demonstrated in ovariectomized (OVX) rodents, there is limited evidence concerning microglial polarization, a key process in brain immune activation, in menopause-related brain.MethodsTherefore, the present study aims to evaluate the polarized microglia in long-term OVX rats and we further explored whether supplementation of ω-3 polyunsaturated fatty acids (PUFA), the pleiotropic bioactive nutrient, is effective in the neurobehavioral changes caused by OVX.ResultsOur data showed that OVX-induced anxiety and depression-like behaviors in rats, accompanied with increased neural apoptosis and microglial activation in the hippocampus. Additionally, OVX enhanced proinflammatory cytokines expression and suppressed the expression of anti-inflammatory cytokine, IL-10. Correspondingly, OVX reinforced NFκB signaling and shifted the microglia from immunoregulatory M2 phenotype to proinflammatory M1 phenotype. Meanwhile, daily supplementation with PUFA suppressed microglial M1 polarization and potentiated M2 polarization in OVX rats. In parallel, PUFA also exerted antidepressant and neuroprotective activities, accompanied with neuroimmune-modulating actions.ConclusionCollectively, the present study firstly demonstrated the disturbed microglial polarization in the OVX brain and provide novel evidence showing the association between the antidepressant actions of PUFA and the restraint neuroinflammatory progression.

Polyunsaturated Fatty Acids and Atherosclerosis: Insights from Pre‐Clinical Studies

Atherosclerosis and its complications are responsible for more global deaths than any other disease. Atherosclerosis is a chronic inflammatory disease of medium and large arteries that can cause clinical complications such as myocardial infarction and cerebrovascular accidents. Current therapies against atherosclerosis mainly target the dyslipidemia associated with the disease and are associated with considerable residual risk for cardiovascular disease together with various side effects. In addition, the outcomes of clinical trials on many pharmaceutical agents against promising therapeutic targets have been disappointing. This has resulted in considerable recent interest on nutraceuticals in the prevention of atherosclerosis and as add‐on with current pharmaceutical therapies. However, nutraceutical research has considerably lagged those on pharmaceuticals on two key aspects, large clinical trials and mechanistic insights. The latter forms the focus of this review in relation to the potential beneficial actions of polyunsaturated fatty acids as identified from pre‐clinical studies.Practical Applications: There is substantial recent interest in the use of nutraceuticals for the prevention and treatment of atherosclerosis. It is therefore important that the molecular mechanisms underlying their protective actions are fully understood and large clinical trials are carried out to evaluate their efficacy. Polyunsaturated fatty acids represent promising anti‐atherogenic agents. This review illuminates on the mechanisms underlying their actions in relation to atherosclerosis as revealed from pre‐clinical studies using in vitro and in vivo model systems.Atherosclerosis is an inflammatory disorder of the vasculature and the underlying cause of cardiovascular disease. Current therapies against atherosclerosis are not fully effective and the outcomes on many promising pharmaceutical agents have been disappointing. This has generated substantial interest in nutraceuticals such as polyunsaturated fatty acids (PUFAs) in the prevention and treatment of this disease. This review describes the actions of omega‐3 and ‐6 PUFAs on key cellular processes associated with atherosclerosis in vitro and the development of the disease in mouse model systems in vivo together with the mechanisms underlying their beneficial effects and studies in humans.

Recent Evidence on the Role of Dietary PUFAs in Cancer Development and Prevention.

Scientific evidence has been accumulated about the effects of polyunsaturated fatty acids (PUFAs) on human health. The hypothesis that n-3 PUFAs might improve the efficiency of anticancer drugs has recently been considered. The role of n-6 PUFAs, in contrast, needs to be better assessed. However, the effective mechanisms of action of PUFAs have not been fully clarified yet. This review aims to report the most updated evidence on the role of n-6 and n-3 PUFAs in the development and treatment of human cancers, focusing on the potential mechanisms by which PUFAs exert their effects. We undertook a structured search in PubMed on February 17th 2017 for peer-reviewed research articles published from 2013. The search syntax used was: PUFA or PUFAs and cancer. Contradictory results were found, most likely due to the genetic background, the different dietary sources used, the interaction among different nutrients, and the tumor subtypes. However, the more recent findings strongly support the use of n-3 PUFAs in cancer prevention and treatment. On the other hand, n-6 PUFAs are often associated with an increased risk of cancer, even if recently their beneficial effects have also been highlighted. N-3 PUFAs may represent a potential therapeutic agent contributing to treat at least some type of human cancers. However, studies with larger sample sizes and longer follow-up times are still needed. To increase the knowledge about how food and nutrition can improve human health it is advisable to deliver an open access nutritional database.

Fatty Acid Profile and Milk Cholesterol of Crossbred Holstein × Zebu Cows Fed on Whole Cottonseed

The objective of this study was to evaluate the effect of whole cottonseed on diets of cows under grazing on fatty acid profile and milk cholesterol. Five crossbred Holstein × Zebu cows were distributed in a 5 × 5 Latin square. Inclusion levels were 0, 6, 12, 18 and 24%. There was a linear decrease in all fatty acids quantified, saturated and monounsaturated (p > 0.05), possibly due to the action of polyunsaturated fatty acids ingested in the diet. There was no influence of treatment on conjugated linoleic acids or cholesterol. It is concluded that, regardless of inclusion level, there is a modification in the milk lipid profile, reducing the concentration of saturated fatty acid, monounsaturated fatty acid, and making it rich in polyunsaturated fatty acids, which are beneficial to health.

Differential action of polyunsaturated fatty acids and eicosanoids on bleomycin-induced cytotoxicity to neuroblastoma cells and lymphocytes.

IntroductionThis study was conducted to examine whether bleomycin-induced growth inhibitory action on human neuroblastoma cells (IMR-32) is influenced by anti-inflammatory metabolites of polyunsaturated fatty acids (PUFAs): lipoxin A4 (LXA4), resolvin D1 and protectin D1 in vitro.Material and methodsThe in vitro study was conducted using monolayer cultures of exponentially growing IMR-32 cells. The effects of various PUFAs and eicosanoids and anti-inflammatory metabolites of PUFAs such as lipoxin A4 (LXA4), resolvin D1 and protectin D1 on the growth of IMR-32 cells and human lymphocytes in vitro were investigated. The potential of PUFAs, eicosanoids and LXA4, resolvin D1 and protectin D1 to modify the growth inhibitory effects of bleomycin was also studied in IMR-32 cells and human lymphocytes.ResultsPUFAs inhibited the growth of IMR-32 cells (EPA > DHA = AA > GLA = ALA > DGLA = LA) significantly (p < 0.001) while prostaglandins were found to be not effective. Bleomycin-induced growth inhibitory action on IMR-32 cells was augmented by PUFAs and its metabolites (p < 0.05). PUFAs and LXA4 did not inhibit the growth of human lymphocytes and bleomycin-induced growth inhibitory action was also not enhanced by these bioactive lipids.ConclusionsBioactive lipids have differential action on normal human lymphocytes and tumor cells in vitro. The apparent lack of effect of PUFAs in combination with bleomycin on the growth of human lymphocytes in comparison to their growth inhibitory action on IMR-32 cells suggests that PUFAs can be used in combination with bleomycin to target tumor cells with little concern over this combination’s effect on the growth of human lymphocytes. Further studies are warranted to evaluate these differential effects under in vivo conditions.

Fish oil and depression: The skinny on fats.

Depression is the leading cause of disability worldwide, and even though many forms of therapy exist, about one third of patients treated with conventional antidepressants do not experience a response. For these reasons, new approaches to treat depression, including fish oil, are being investigated. Fish oil is known to have many beneficial side effects, and clinical trials demonstrate that supplementation with fish oil is beneficial in the management of depression. Fish oil contains omega-3 polyunsaturated fatty acids (PUFA), and there are several mechanisms by which PUFAs are thought to induce an antidepressant effect, including anti-inflammatory action and direct effects on membrane properties. This review will analyze and evaluate the clinical trials surrounding fish oil use in the treatment of depression, and will also review the likely sites of action of PUFAs at the cell membrane with special attention being placed on lipid rafts and G-proteins.

Омега-3 полиненасыщенные жирные кислоты при введении кормящим крысам модулируют поведение крысят, перенесших стрессирование путем многократного введения физиологического раствора в неонатальном периоде

Омега-3 полиненасыщенные жирные кислоты (ПНЖК) могут оказывать антидепрессивное, анксиолитическое и антистрессорное действие, однако данные противоречивы. Недавно на модели тревожно-депрессивного состояния, индуцированного неонатальным действием ингибитора дипептидилпептидазы IV дипротина А, мы показали, что омега-3 ПНЖК наряду с антидепрессивным действием также повышают тревожность у крысят опытной группы и нарушают эмоциональное поведение контрольных животных, подвергнутых многократному введению физиологического раствора (ФР). Цель работы - изучение влияния омега-3 ПНЖК при их введении кормящим крысам Вистар, на эмоционально-мотивационное поведение крысят, подвергнутых стрессогенной процедуре многократного введения ФР на 2-й - 3-й неделях постнатального развития, и интактных животных в динамике взросления. Методика. Омега-3 ПНЖК вводили крысам в период лактации перорально в дозе 0,3 г/кг в течение 28 дней. ФР вводили внутрибрюшинно в период с 5-го по 18-й дни постнатального развития. Эмоционально-мотивационное поведение крыс оценивали с помощью общепринятых методов. Результаты. Омега-3 ПНЖК предотвращали появление признаков депрессивноподобного поведения и оказывали психостимулирующее действие на животных, перенесших стрессирование в раннем неонатальном периоде. Омега-3 ПНЖК также нормализовали вызванные стрессом нарушения социального взаимодействия неагрессивного характера у крыс подросткового возраста и взрослых животных, однако способствовали повышению агрессивности у взрослых интактных крыс. Независимо от факта стрессирования, омега-3 ПНЖК по разным показателям тревожности оказывали как анксиолитическое, так и анксиогенное действие на крыс-подростков, тогда как у взрослых животных обнаружено только их анксиогенное влияние. У стрессированных и интактных взрослых крыс омега-3 ПНЖК вызывали снижение ориентировочно-исследовательской активности. Заключение. Омега-3 ПНЖК в условиях их приема кормящими самками, оказывают как позитивное, так и негативное влияние на эмоционально-мотивационное поведение потомства, перенесшего в неонатальном периоде стрессирование путем многократного введения ФР. Эффекты омега-3 ПНЖК различаются у животных подросткового и взрослого возраста. Угнетающее действие на психомоторную активность и анксиогенное влияние омега-3 ПНЖК проявляется как у стрессированных, так и у интактных крыс, что следует учитывать при разработке подходов к терапии психоневрологических расстройств с использованием омега-3 ПНЖК.Omega-3 polyunsaturated fatty acids (PUFAs) may exert antidepressant, anxiolytic and anti-stress effects, but the data are contradictory. Recently, using the model of experimental anxiety-depressive disorder caused by the neonatal action of an inhibitor of dipeptidyl peptidase IV diprotin A, we have shown that omega-3 PUFAs along with an antidepressant effect also increase anxiety in the rat pups in the experimental group and disrupt emotional behavior in control animals subjected to repeated administration of saline. The purpose of this work was to study the effects of omega-3 PUFAs when administered to the lactating Wistar rats, on the emotional and motivational behavior of the rat pups exposed to the procedure of the repeated saline administration on second - third weeks of postnatal development and intact rats in the dynamics of growing up. Methods. Omega-3 PUFAs were administered to lactating rats at a dose 0.3 g/kg, per os, for 28 days. Saline was administered intraperitoneally on postnatal days 5-18. We assessed emotional and motivational behavior using conventional methods. Results. Omega-3 PUFAs prevented the appearance of the symptoms of depressive-like behavior and exerted a psycho stimulative effect on the animals that underwent stress in the early neonatal period. Omega-3 PUFAs also normalized stress-related impairment of social non-aggressive interaction in adolescent and adult rats but promoted increased aggression in adult intact rats. Regardless of whether the stress, omega-3 PUFAs exhibited both anxiolytic and anxiogenic effects for different anxiety indicators in adolescent rats, whereas in adult animals only anxiogenic effect was detected. In adult stressed and intact rats, omega-3 PUFAs caused a decrease in exploratory activity. Conclusion. Omega-3 PUFAs when administered to the lactating females, exert both positive and negative effects on the emotional and motivational behavior of the offspring, which underwent stress by repeated saline administration in the neonatal period. Omega-3 PUFAs action differs in adolescent and adult rats. The inhibitory effect on psychomotor activity and anxiogenic effects of omega-3 PUFAs appear in both stressed and intact rats that should be taken into account when developing approaches to the treatment of psycho-neurological disorders using omega-3 PUFAs.

The pro- or antiarrhythmic actions of polyunsaturated fatty acids and of cholesterol.

In this review, the pro- and anti-arrhythmic effects of a diet rich in fish oil fatty acids and of hypercholesterolemia will be discussed in relation to two major mechanisms of arrhythmogenesis (triggered activity and re-entry). Whereas a diet rich in fish oil is pro-arrhythmic in relation to re-entry based arrhythmias (as occur in acute myocardial ischemia) and anti-arrhythmic in relation to triggered activity based arrhythmias (as occur in heart failure), the reverse is true for hypercholesterolemia. Changing the lipid composition of cardiomyocytes likely has powerful pro- or anti-arrhythmic consequences, depending on the mechanism of arrhythmias, and has corresponding therapeutic potential.

Fish oil supplementation attenuates neuroinflammation and alleviates depressive-like behavior in rats submitted to repeated lipopolysaccharide.

Depression is frequently associated with inflammation, whereas omega-3 polyunsaturated fatty acids (PUFAs) primarily found in fish oil possess anti-inflammatory properties. Although converging studies suggest an antidepressant effect of PUFAs, there is limited evidence directly linking the neuro-immune modulating features of PUFAs to the antidepressant actions. Therefore, we assessed the effects of fish oil (FO) supplementation on behavioral changes, inflammatory cytokine expression and oxidative reactions in frontal cortex and hippocampus of rats following repeated peripheral immune challenge by lipopolysaccharide (LPS) for 2weeks (500μg/kg every other day). Repeated LPS administration induced the rats to a depressive-like state and increased mRNA expression of pro-inflammatory cytokines, including 1L-1β, 1L-6 and TNF-α, in frontal cortex and hippocampus. FO supplementation attenuated the LPS-induced abnormal behavior and brain inflammatory response. Concurrent with the antidepressant action, FO also reduced LPS-induced oxidative reactions and neural apoptosis in the rat brain, as evidenced by decreased malondialdehyde (MDA) production, increased catalase activities and inhibited pro-apoptotic protein Bax mRNA expression. In addition, FO inhibited activation of NF-κB and iNOS induced by LPS. Interestingly, we found FO suppressed the activation of the inflammasome NLRP3 and ionotropic purinergic receptor P2X7R evoked by LPS, suggesting a potential anti-inflammatory mechanism for PUFAs. Besides, FO also restored the LPS-induced neurochemical disturbance, especially the balance between serotonin and kynurenine branches of tryptophan metabolism, which is tightly associated with depression. These findings provide novel insights into the antidepressant action of PUFAs and further strengthen the link between inflammation and depression.

Polyunsaturated fatty acids inhibit Kv1.4 by interacting with positively charged extracellular pore residues.

Polyunsaturated fatty acids (PUFAs) modulate voltage-gated K(+) channel inactivation by an unknown site and mechanism. The effects of ω-6 and ω-3 PUFAs were investigated on the heterologously expressed Kv1.4 channel. PUFAs inhibited wild-type Kv1.4 during repetitive pulsing as a result of slowing of recovery from inactivation. In a mutant Kv1.4 channel lacking N-type inactivation, PUFAs reversibly enhanced C-type inactivation (Kd, 15-43 μM). C-type inactivation was affected by extracellular H(+) and K(+) as well as PUFAs and there was an interaction among the three: the effect of PUFAs was reversed during acidosis and abolished on raising K(+) Replacement of two positively charged residues in the extracellular pore (H508 and K532) abolished the effects of the PUFAs (and extracellular H(+) and K(+)) on C-type inactivation but had no effect on the lipoelectric modulation of voltage sensor activation, suggesting two separable interaction sites/mechanisms of action of PUFAs. Charge calculations suggest that the acidic head group of the PUFAs raises the pKa of H508 and this reduces the K(+) occupancy of the selectivity filter, stabilizing the C-type inactivated state.