Classes Of Polyunsaturated Fatty Acids Research Articles

Supercritical extract from the Japanese sea brown algae <i>Undaria pinnatifida</i> as a source of bioactive compounds

Bioactive compounds contained in algae have practical applications in the pharmaceutical industry, production of human food and animal feed, and other fields. Since brown algae contain a wide range of bioactive substances, producing high-quality and chemically safe extracts on their basis is an urgent task. This study was aimed at characterization of supercritical extract from the corresponding algae, as well as the identification and evaluation of the content of bioactive compounds. The content of carotenoids, phenolic compounds and mannitol was determined by UV-Vis spectroscopy; a fatty acid analysis was carried out by GLPC; the qualitative composition of carotenoids and phenolic compounds was analyzed by HPLC. Supercritical CO2 extraction of the brown alga U. rinnatifida with EtOH as a polar modifier is characterized by high ejection efficiency of fatty acids, phenolic compounds and carotenoids. The latter profile of the collected supercritical extract consists of 14 representatives. In particular, fucoxanthin (58.1% of the sum), zeaxanthin (12.6% of the sum), and fucoxanthinol (14.5% of the sum) are the most abundant compounds. Palmitic acid, oleic acid, arachidonic acid, and eicosapentaenoic acids are the main of the 20 fatty acids found in the corresponding extract. However, the class of polyunsaturated fatty acids is predominant, which content of the ώ-6 and ώ-3 groups does not differ significantly. The total content of phenolic compounds is 13.45+0.43 mg/g of gallic acid equivalent. For instance, the most represented phenolic substances are epicatechin, epigallocatechin gallate, syringic acid, coumaric acid, ferulic acid and salicylic acid.

A high ratio of linoleic acid (n-6 PUFA) to alpha-linolenic acid (n-3 PUFA) adversely affects early stage of human neuronal differentiation and electrophysiological activity of glutamatergic neurons in vitro.

Introduction: There is a growing interest in the possibility of dietary supplementation with polyunsaturated fatty acids (PUFAs) for treatment and prevention of neurodevelopmental and neuropsychiatric disorders. Studies have suggested that of the two important classes of polyunsaturated fatty acids, omega-6 (n-6) and omega-3 (n-3), n-3 polyunsaturated fatty acids support brain development and function, and when used as a dietary supplement may have beneficial effects for maintenance of a healthy brain. However, to date epidemiological studies and clinical trials on children and adults have been inconclusive regarding treatment length, dosage and use of specific n-3 polyunsaturated fatty acids. The aim of this study is to generate a simplified in vitro cell-based model system to test how different n-6 to n-3 polyunsaturated fatty acids ratios affect human-derived neurons activity as a cellular correlate for brain function and to probe the mechanism of their action. Methods: All experiments were performed by use of human induced pluripotent stem cells (iPSCs). In this study, we examined the effect of different ratios of linoleic acid (n-6) to alpha-linolenic acid in cell growth medium on induced pluripotent stem cell proliferation, generation of neuronal precursors and electrophysiology of cortical glutamatergic neurons by multielectrode array (MEA) analysis. Results: This study shows that at a n-6:n-3 ratio of 5:1 polyunsaturated fatty acids induce stem cell proliferation, generating a large increase in number of cells after 72h treatment; suppress generation of neuronal progenitor cells, as measured by decreased expression of FOXG1 and Nestin in neuronal precursor cells (NPC) after 20days of development; and disrupt neuronal activity in vitro, increasing spontaneous neuronal firing, reducing synchronized bursting receptor subunits. We observed no significant differences for neuronal precursor cells treated with ratios 1:3 and 3:1, in comparison to 1:1 control ratio, but higher ratios of n-6 to n-3 polyunsaturated fatty acids adversely affect early stages of neuronal differentiation. Moreover, a 5:1 ratio in cortical glutamatergic neurons induce expression of GABA receptors which may explain the observed abnormal electrophysiological activity.

Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids

N-acyl taurines (NATs) are bioactive lipids with emerging roles in glucose homeostasis and lipid metabolism. The acyl chains of hepatic and biliary NATs are enriched in polyunsaturated fatty acids (PUFAs). Dietary supplementation with a class of PUFAs, the omega-3 fatty acids, increases their cognate NATs in mice and humans. However, the synthesis pathway of the PUFA-containing NATs remains undiscovered. Here, we report that human livers synthesize NATs and that the acyl-chain preference is similar in murine liver homogenates. In the mouse, we found that hepatic NAT synthase activity localizes to the peroxisome and depends upon an active-site cysteine. Using unbiased metabolomics and proteomics, we identified bile acid-CoA:amino acid N-acyltransferase (BAAT) as the likely hepatic NAT synthase in vitro. Subsequently, we confirmed that BAAT knockout livers lack up to 90% of NAT synthase activity and that biliary PUFA-containing NATs are significantly reduced compared with wildtype. In conclusion, we identified the in vivo PUFA-NAT synthase in the murine liver and expanded the known substrates of the bile acid-conjugating enzyme, BAAT, beyond classic bile acids to the synthesis of a novel class of bioactive lipids.

Polyunsaturated Fatty Acids as Dietary Supplements: Biological Activities and Sources

Polyunsaturated fatty acids (PUFAs) have been used as dietary supplements for quite some time with various health claims. Major dietary PUFAs are classified as omega-3 and omega-6 based on their structure, and these fatty acids are considered essential nutrients. The two classes of PUFAs, although structurally similar, present different biological activities that can be beneficial or detrimental to humans. Some of these biological activities have been known for a long time, while others are emerging from the plethora of dietary studies done on PUFAs. Yet many of the health claims for PUFAs are still debated, with the findings being conflicting. This review summarizes our current knowledge on the biological activities of PUFAs and discusses the dietary sources available. In light of new dietary recommendations, PUFA consumption is on the rise, so new dietary sources for these fatty acids are needed.

Plasma and erythrocyte membrane phospholipids and fatty acids in Italian general population and hemodialysis patients

BackgroundDyslipidemia and abnormal phospholipid metabolism are frequent in uremic patients and increase their risk of cardiovascular disease (CVD): ω-3 polyunsaturated fatty acids (PUFAs) may reduce this risk in the general population. In this study we compared the plasma and erythrocyte cell membrane composition of PUFAs in a group of Caucasian hemodialysis (HD) patients and in a control group of healthy subjects and evaluated the erythrocyte/cell membrane fatty acid ratio as a marker of the dietary intake of phospholipids. The relationship between ω-3 and ω-6 fatty acids and the possible differences in PUFAs concentrations were also investigated.Methods and resultsAfter obtaining a fully informed consent, a total of ninety-nine HD patients and 160 non uremic control subjects from “Tor Vergata” University Hospital were enrolled into the study. None of them took antioxidant drugs or dietary supplements for at least 90 days prior to the observation. Blood samples were analysed by gas-chromatographic coupled to a mass spectrometric detector.The daily intake of total calories, proteins, lipids and carbohydrates is significantly lower in HD patients than in controls (p < 0.001). Most plasma and erythrocyte PUFA were also reduced significantly in HD patients (p < 0.001).ConclusionsOur results suggest that many classes of PUFAs are lacking in HD patients, due to the removal of nutrients during the dialysis and to persistent malnutrition. A dietary treatment addressed to increase plasma ω-3 PUFAs and to optimize ω-6/ω-3 ratio may exert a protective action and reduce the risk of CVD in HD patient.

Nutritional Proteomics: Investigating molecular mechanisms underlying the health beneficial effect of functional foods

Objective: We introduce a new technical and conceptual term “nutritional proteomics” by identifying and quantifying the proteins and their changes in a certain organ or tissue dependent on the food intake by utilizing a mass spectrometry-based proteomics technique.Purpose: Food intake is essentially important for every life on earth to sustain the physical as well as mental functions. The outcome of food intake will be manifested in the health state and its dysfunction. The molecular information about the protein expression change caused by diets will assist us to understand the significance of functional foods. We wish to develop nutritional proteomics to promote a new area in functional food studies for a better understanding of the role of functional foods in health and disease.Methods: We chose two classes of food ingredients to show the feasibility of nutritional proteomics, omega-3 polyunsaturated fatty acids and omega-6 polyunsaturated fatty acids both of which are involved in the inflammation/anti-inflammation axis. Each class of the polyunsaturated fatty acids was mixed in mouse chow respectively. The liver tissue of mice fed with omega-3 diet or omega-3 diet was analyzed by the state-of-the-art shotgun proteomics using nano-HPLC-ESI-MS/MS. The data were analyzed by the number of differentially expressed proteins that were guaranteed by 1% false discovery rate for protein identification and by the statistical significance of variance evaluated by p-value in two-tailed distribution analysis better than 0.05 (n=4). The differential pattern of protein expression was characterized with Gene Ontology designation.Results: The data analysis of the shotgun nutritional proteomics identified 2,810 proteins that are validated with 1% FDR. Among these 2,810 proteins, 125 were characterized with statistical significance of variance (p&lt;0.05; n=4)between the omega-3 diet and the omega-6 diet by two-tailed distribution analysis. The results illustrate that the dietary influence of omega-3 and omega-6 on protein expression is eminent with the proteins directly responsible for catalytic activity in the “Molecular Function” category, totaling 192 proteins, of Gene Ontology designation. In a similar analysis with regard to the “Cellular Localization” category, protein expression changed the most in the sub-categories of “Cytoplasm”, “Membrane”, “Nucleus”, and “Mitochondrion”, totaling 221 proteins. The same analysis with regard to “Biological Process” considering the top four categories, i.e., “Metabolic process”, “Regulation of biological (process)”, “Response to stimulus”, and “Transport” also indicated significant alteration of 182 proteins. These results illustrate a robust influence of dietary elements, omega-3 or omega-6 polyunsaturated fatty acids, on the protein expression in mouse liver.Conclusions: Application of nutritional proteomics to the dietary effect of omega-3 polyunsaturated fatty acids compared to that of omega-6 on mouse liver revealed; 1) significant number of proteins are altered between the two diets dependent on the classes of polyunsaturated fatty acids, omega-3 or omega-6, in the diet. The change of protein expression is likely to carry the molecular information that we could possibly decipher, leading to a better understanding of the role of omega-3 polyunsaturated fatty acids in inflammatory/anti-inflammatory process. The results corroborate the concept and utility of nutritional proteomics that should be developed as a part of functional food studies with regard to other dietary types.Keywords: Nutritional proteomics, functional foods, mass spectrometry, genome database, cellular signaling, omega-3 and omega-6 polyunsaturated fatty acids

Dietary n-3 Polyunsaturated Fatty Acids and the Paradox of Their Health Benefits and Potential Harmful Effects

There is some evidence to support the toxicity of polyunsaturated fatty acids (PUFAs) and their oxidative products, suggesting their involvement in the pathogenesis of different chronic diseases, including cancer. It has been shown that products of PUFA oxidation may exert a carcinogenic action by forming mutagenic adducts with DNA. However, a large amount of evidence accumulated over several decades has indicated the beneficial effects of administration of n-3 PUFAs in the prevention and therapy of a series of diseases. In particular, there is much evidence that n-3 PUFAs exert anti-inflammatory and antineoplastic effects, whereas n-6 PUFAs promote inflammation and carcinogenesis. In our tissues, both of the two classes of PUFAs can be converted into bioactive products, incorporated into membrane phospholipids or bound to membrane receptors, where they may alter, often in opposite ways, transduction pathways and affect important biological processes, such as cell death and survival, inflammation, and neo-angiogenesis. In the present review, we intend to shed light on the paradox of the coexisting healthy and toxic effects of n-3 PUFAs, focusing on their possible pro-oxidant cytotoxic and carcinogenic effect, in order to understand if their increased intake, recommended by a number of health agencies worldwide and promoted by nutraceutical producers, may or may not represent a hazard to human health.

Long-Chain Polyunsaturated Fatty Acids Promote Paclitaxel Cytotoxicity via Inhibition of the MDR1 Gene in the Human Colon Cancer Caco-2 Cell Line

Objective: Accumulating evidence in both humans and animal models indicates that dietary intake of long-chain polyunsaturated fatty acids (PUFAs) can improve response to chemotherapy. The intent of this study was to determine the mechanisms by which PUFAs affect the response to anticancer chemotherapy.Methods: Human colorectal cancer cell line Caco-2 was used as a model system in this study. Caco-2 cells were treated with different concentrations of three PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA). Real-time polymerase chain reaction was used to determine mdr1 gene (codes for P-glycoprotein [P-gp]) expression. Western blotting and calcein-acetoxymethylester efflux assay were used for P-gp expression and functional evaluation, respectively. Furthermore, apoptosis assay was conducted by adding PUFAs with paclitaxel to confirm the synergetic effect. Finally, gene expression of nuclear receptors CAR and PXR were estimated to evaluate the possible mechanisms.Results: Both classes of PUFAs, omega-3 (ω-3) and omega-6 (ω-6), can cause a modest but very reproducible reduction of gene expression, protein production, and pump activity of MDR1. Incubation of cells with PUFAs greatly enhanced the cytotoxicity of the anticancer drug paclitaxel, manifested mainly through enhanced paclitaxel-induced apoptosis. Furthermore, PUFAs increased the messenger RNA (mRNA) levels of the nuclear receptors CAR and PXR, thus implicating these two transcription factors as cellular targets of PUFAs in cells but not directly affecting MDR1 regulation.Conclusions: Our results suggest that inhibition of the multidrug resistance MDR1/P-gp is one mechanism through which dietary polyunsaturated fatty acids exert a synergetic effect on the response of tumor cells to anticancer drugs.

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

Linoleic acid (18:2ω6) and α-linolenic acid (18:3ω3) represent the parent fats of the two main classes of polyunsaturated fatty acids: the ω-6 (n-6) and the ω-3 (n-3) fatty acids, respectively. Linoleic acid and α-linolenic acid both give rise to other long-chain fatty acid derivatives, including γ-linolenic acid and arachidonic acid (ω-6 fatty acids) and docosahexaenoic acid and eicosapentaenoic acid (ω-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-α, interferon-γ, 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.

Essential fatty acids, DHA and human brain

Essential fatty acids cannot be synthesized in the body but they are required for maintenance of optimal health. There are two classes of polyunsaturated fatty acids (PUFAs)--omega-6 and omega-3. The parent omega-6 fatty acid, linoleic acid (LA) is desaturated in the body to form arachidonic acid while parent omega-3 fatty acid alpha-linolenic acid (ALA) is desaturated by microsomal enzyme system through a series of metabolic steps to form eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA). But there is a limited metabolic capability during early life to metabolize PUFAs to more active long-chain fatty acids. There is a critical role of EFAs and their metabolic products for maintenance of structural and functional integrity of central nervous system and retina. Most of the brain growth is completed by 5-6 years of age. At birth brain weight is 70% of an adult, 15% brain growth occurs during infancy and remaining brain growth is completed during preschool years. DHA is the predominant structural fatty acid in the central nervous system and retina and its availability is crucial for brain development. It is recommended that the pregnant and nursing woman should take at least 2.6 g of omega-3 fatty acids and 100-300 mg of DHA daily to look after the needs of her fetus and suckling infant. The follow-up studies have shown that infants of mothers supplemented with EFAs and DHA had higher mental processing scores, psychomotor development, eye-hand coordination and stereo acuity at 4 years of age. Intake of EFAs and DHA during preschool years may also have a beneficial role in the prevention of attention deficit hyperactivity disorder (ADHD) and enhancing learning capability and academic performance.

Dietary fats and membrane function: implications for metabolism and disease

Lipids play varied and critical roles in metabolism, with function dramatically modulated by the individual fatty acid moities in complex lipid entities. In particular, the fatty acid composition of membrane lipids greatly influences membrane function. Here we consider the role of dietary fatty acid profile on membrane composition and, in turn, its impact on prevalent disease clusters of the metabolic syndrome and mental illness. Applying the classical physiological conformer-regulator paradigm to quantify the influence of dietary fats on membrane lipid composition (i.e. where the membrane variable is plotted against the same variable in the environment--in this case dietary fats), membrane lipid composition appears as a predominantly regulated parameter. Membranes remain relatively constant in their saturated (SFA) and monounsaturated (MUFA) fatty acid levels over a wide range of dietary variation for these fatty acids. Membrane composition was found to be more responsive to n-6 and n-3 polyunsaturated fatty acid (PUFA) levels in the diet and most sensitive to n-3 PUFA and to the n-3/n-6 ratio. These differential responses are probably due to the fact that both n-6 and n-3 PUFA classes cannot be synthesised de novo by higher animals. Diet-induced modifications in membrane lipid composition are associated with changes in the rates of membrane-linked cellular processes that are major contributors to energy metabolism. For example, in the intrinsic activity of fundamental processes such as the Na+/K+ pump and proton pump-leak cycle. Equally, dietary lipid profile impacts substantially on diseases of the metabolic syndrome with evidence accruing for changes in metabolic rate and neuropeptide regulation (thus influencing both sides of the energy balance equation), in second messenger generation and in gene expression influencing a range of glucose and lipid handling pathways. Finally, there is a growing literature relating changes in dietary fatty acid profile to many aspects of mental health. The understanding of dietary lipid profile and its influence on membrane function in relation to metabolic dysregulation has exciting potential for the prevention and treatment of a range of prevalent disease states.

Role of Ca2+-independent phospholipase A2 and n−3 polyunsaturated fatty acid docosahexaenoic acid in prostanoid production in brain: perspectives for protection in neuroinflammation

Various diseases of the central nervous system are characterized by induction of inflammatory events, which involve formation of prostaglandins. Production of prostaglandins is regulated by activity of phospholipases A2 and cyclooxygenases. These enzymes release the prostaglandin precursor, the n−6 polyunsaturated fatty acid, arachidonic acid and oxidize it into prostaglandin H2. Docosahexaenoic acid, which belongs to the n−3 class of polyunsaturated fatty acids, was shown to reduce production of prostaglandins after in vivo and in vitro administration. Nevertheless, the fact that in brain tissue cellular phospholipids naturally have a uniquely high content of docosahexaenoic acid was ignored so far in studies of prostaglandin formation in brain tissue. We consider the following possibilities: docosahexaenoic acid might attenuate production of prostaglandins by direct inhibition of cyclooxygenases. Such inhibition was found with the isolated enzyme. Another possibility, which has been already shown is reduction of expression of inducible cyclooxygenase-2. Additionally, we propose that docosahexaenoic acid could influence intracellular Ca2+ signaling, which results in changes of activity of Ca2+-dependent phospholipase A2, hence reducing the amount of arachidonic acid available for prostaglandin production. Astrocytes, the main type of glial cells in the brain control the release of arachidonic acid, docosahexaenoic acid and the formation of prostaglandins. Our recently obtained data revealed that the release of arachidonic and docosahexaenoic acids in astrocytes is controlled by different isoforms of phospholipase A2, i.e. Ca2+-dependent phospholipase A2 and Ca2+-independent phospholipase A2, respectively. Moreover, the release of arachidonic and docosahexaenoic acids is differently regulated through Ca2+- and cAMP-dependent signal transduction pathways. Based on analysis of the current literature and our own data we put forward the hypothesis that Ca2+-independent phospholipase A2 and docosahexaenoic acid are promising targets for treatment of inflammatory related disorders in brain. We suggest that Ca2+-independent phospholipase A2 and docosahexaenoic acid might be crucially involved in brain-specific regulation of prostaglandins.

4-Hydroxynonenal in the pathomechanisms of oxidative stress.

Here we review the current knowledge on the biochemistry and molecular pathology of oxidative stress with specific regard to a major aldehydic end-product stemming from peroxidation of biomembranes, that is 4-hydroxynonenal (HNE). This multifunctional molecule, which derives from the most represented class of polyunsaturated fatty acids in the membranes, is potentially able to undergo a number of reactions with proteins, phospholipids, and nucleic acids. Despite an active metabolism in most of the cell types, HNE can be detected in several biological tissues by means of sufficiently precise methods, although with different sensitivity. In particular, relatively high steady-state levels of HNE are often detectable in a large variety of human disease processes, pointing to some involvement of the aldehyde in their pathogenesis. Among the prominent pathobiochemical effects of HNE is its remarkable stimulation of fibrogenesis and inflammation, which indicates a potential contribution of the aldehyde to the pathogenesis of several chronic diseases, whose progression is indeed supported by inflammatory reactions and characterized by fibrosis. Further, of interest appears to be the ability of HNE to modulate cell proliferation through interference with the activity of cyclins and protein kinases and with the apoptotic machinery. Finally, on the basis of the already achieved evidence, pursuing investigation of the role of HNE in signal transduction and gene expression seems very promising.

Human Requirement for N-3 Polyunsaturated Fatty Acids

The diet of our ancestors was less dense in calories, being higher in fiber, rich in fruits, vegetables, lean meat, and fish. As a result, the diet was lower in total fat and saturated fat, but contained equal amounts of n-6 and n-3 essential fatty acids. Linoleic acid (LA) is the major n-6 fatty acid, and alpha-linolenic acid (ALA) is the major n-3 fatty acid. In the body, LA is metabolized to arachidonic acid (AA), and ALA is metabolized to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The ratio of n-6 to n-3 essential fatty acids was 1 to 2:1 with higher levels of the longer-chain polyunsaturated fatty acids (PUFA), such as EPA, DHA, and AA, than today's diet. Today this ratio is about 10 to 1:20 to 25 to 1, indicating that Western diets are deficient in n-3 fatty acids compared with the diet on which humans evolved and their genetic patterns were established. The n-3 and n-6 EPA are not interconvertible in the human body and are important components of practically all cell membranes. The N-6 and n-3 fatty acids influence eicosanoid metabolism, gene expression, and intercellular cell-to-cell communication. The PUFA composition of cell membranes is, to a great extent, dependent on dietary intake. Therefore, appropriate amounts of dietary n-6 and n-3 fatty acids need to be considered in making dietary recommendations. These two classes of PUFA should be distinguished because they are metabolically and functionally distinct and have opposing physiological functions; their balance is important for homeostasis and normal development. Studies with nonhuman primates and human newborns indicate that DHA is essential for the normal functional development of the retina and brain, particularly in premature infants. A balanced n-6/n-3 ratio in the diet is essential for normal growth and development and should lead to decreases in cardiovascular disease and other chronic diseases and improve mental health. Although a recommended dietary allowance for essential fatty acids does not exist, an adequate intake (AI) has been estimated for n-6 and n-3 essential fatty acids by an international scientific working group. For Western societies, it will be necessary to decrease the intake of n-6 fatty acids and increase the intake of n-3 fatty acids. The food industry is already taking steps to return n-3 essential fatty acids to the food supply by enriching various foods with n-3 fatty acids. To obtain the recommended AI, it will be necessary to consider the issues involved in enriching the food supply with n-3 PUFA in terms of dosage, safety, and sources of n-3 fatty acids.

Essentiality of fatty acids.

All fatty acids have important functions, but the term "essential" is applied only to those polyunsaturated fatty acids (PUFA) that are necessary for good health and cannot be completely synthesized in the body. The need for arachidonic acid, which is utilized for eicosanoid synthesis and is a constituent of membrane phospholipids involved in signal transduction, is the main reason why the n-6 class of PUFA are essential. Physiological data indicate that n-3 PUFA also are essential. Although eicosapentaenoic acid also is a substrate for eicosanoid synthesis, docosahexaenoic acid (DHA) is more likely to be the essential n-3 constituent because it is necessary for optimal visual acuity and neural development. DHA is present in large amounts in the ethanolamine and serine phospholipids, suggesting that its function involves membrane structure. Because the metabolism of n-6 PUFA is geared primarily to produce arachidonic acid, only small amounts of 22-carbon n-6 PUFA are ordinarily formed. Thus, the essentiality of n-3 PUFA may be due to their ability to supply enough 22-carbon PUFA for optimal membrane function rather than to a unique biochemical property of DHA.

The electrical and mechanical response of adult guinea pig and rat ventricular myocytes to ω3 polyunsaturated fatty acids

Single adult guinea-pig and rat ventricular cardiac myocytes were used to study the effects of two members of the ω3 class of polyunsaturated fatty acids, docosahexaenoic acid and eicosapentaenoic acid, on the electrical and mechanical activity of cardiac muscle. Docosahexaenoic acid and eicosapentaenoic acid reduced the electrical excitability of both guinea-pig and rat cells in a dose-dependent manner. Both agents produced a dose-dependent negative inotropic response in guinea-pig cells but in the rat cells there was first a dose-dependent positive inotropic effect at low concentrations (<10 μM) followed by a negative inotropic effect at higher concentrations (>10 μM). Possible mechanisms by which these agents affect contraction were studied using conventional electrophysiological techniques. The polyunsaturated fatty acids reduced the action potential duration and the plateau potential of the guinea-pig cells in a simple, dose-dependent manner. In contrast, the effect on the rat action potential mirrored the inotropic effect. At low concentrations (<10 μM) there was a concentration-dependent increase in action potential duration followed by a concentration-dependent decrease at higher concentrations (>10 μM). Both polyunsaturated fatty acids decreased the fast Na + current and the L-type Ca 2+ current in a concentration-dependent but not use-dependent manner in cells from both species. In the rat cells these agents inhibited the transient outward current resulting in an increase in the duration of the rat action potential. The effects of polyunsaturated fatty acids on the Ca 2+, Na + and K + currents underlie these changes in the action potentials in guinea-pig and rat heart cells. The effects on the L-type Ca 2+ current and action potential duration can also explain both the simple negative inotropic effects of the agents on the guinea-pig cells and the more complex effects on the rat cells. These effects of polyunsaturated fatty acids on membrane currents may account for their anti-arrhythmic properties.

Fish consumption, fish oil, lipids, and coronary heart disease

Reducing intake of saturated fat and dietary cholesterol and avoiding excess calories, which can lead to obesity, remain the cornerstore of the dietary approach to decreasing risk of atherosclerotic vascular disease. During the past 20 years, however, there has been renewed interest in other dietary components that might favorably improve lipid profiles and reduce risk of coronary heart disease (CHD). Fish and fish oil, rich sources of omega-3 fatty acids, have sparked intense interest in both epidemiological studies, which suggest a favorable effect on CHD, and metabolic ward studies, which show a striking improvement in lipid profiles in hyperlipidemic patients. Confusion has resulted from clinical trials of fish oil in patients with CHD, which did not corroborate early observational findings, and newer results, which suggest clinical benefit due to a mechanism independent of lipid effects. Fish and other marine life are rich sources of a special class of polyunsaturated fatty acids known as the omega-3 or n-3 fatty acids.1 2 They are so named because the first of the several double bonds occur three carbon atoms away from the terminal end of the carbon chain. The three n-3 polyunsaturated fatty acids (n-3 PUFAs) are alpha linolenic acid (LNA), eicosapentenoic acid (EPA), and docosahexenoic acid (DHA). LNA is an 18–carbon chain fatty acid with three double bonds; in the form of tofu, soybean, and canola oil and nuts, it is an important plant-based source of n-3 PUFA for vegetarians and non–seafood eaters. EPA and DHA are very long–chain fatty acids obtained from marine sources. These, along with n-6 polyunsaturated fatty acids (n-6 PUFAs) that cannot be synthesized from nonlipid precursors such as linoleic acid, are considered essential fatty acids that must be consumed in the diet. The n-6 PUFAs are obtained primarily from plant sources, especially seeds. Arachidonic acid is …

Fish consumption, fish oil, lipids, and coronary heart disease.

Reducing intake of saturated fat and dietary cholesterol and avoiding excess calories, which can lead to obesity, remain the cornerstore of the dietary approach to decreasing risk of atherosclerotic vascular disease. During the past 20 years, however, there has been renewed interest in other dietary components that might favorably improve lipid profiles and reduce risk of coronary heart disease (CHD). Fish and fish oil, rich sources of omega-3 fatty acids, have sparked intense interest in both epidemiological studies, which suggest a favorable effect on CHD, and metabolic ward studies, which show a striking improvement in lipid profiles in hyperlipidemic patients. Confusion has resulted from clinical trials of fish oil in patients with CHD, which did not corroborate early observational findings, and newer results, which suggest clinical benefit due to a mechanism independent of lipid effects. Fish and other marine life are rich sources of a special class of polyunsaturated fatty acids known as the omega-3 or n-3 fatty acids.1 2 They are so named because the first of the several double bonds occur three carbon atoms away from the terminal end of the carbon chain. The three n-3 polyunsaturated fatty acids (n-3 PUFAs) are alpha linolenic acid (LNA), eicosapentenoic acid (EPA), and docosahexenoic acid (DHA). LNA is an 18–carbon chain fatty acid with three double bonds; in the form of tofu, soybean, and canola oil and nuts, it is an important plant-based source of n-3 PUFA for vegetarians and non–seafood eaters. EPA and DHA are very long–chain fatty acids obtained from marine sources. These, along with n-6 polyunsaturated fatty acids (n-6 PUFAs) that cannot be synthesized from nonlipid precursors such as linoleic acid, are considered essential fatty acids that must be consumed in the diet. The n-6 PUFAs are obtained primarily from plant sources, especially seeds. Arachidonic acid is …

Phospholipid fatty acyl distribution of three fungi indicates positional specificity for n‐6vs. n‐3 fatty acids

AbstractPhospholipids of the fungiConidobolus nanodes, Entomophthora exitalis andSaprolegnia parasitica were extracted and analyzed. The phospholipid content was the same (2.4%) for the three species and was independent of the total lipid content. Phospholipase A2 degradation of individual phospholipid classes showed an asymmetrical distribution of polyunsaturated fatty acids (PUFA) between the two fatty acyl positions of glycerol. There was a predominance of n‐6 PUFA at position 2 and a predominance of n‐3 PUFA at position 1. WithC. nanodes andE. exitalis, 20∶5n−3 is derived from 18∶3n−3 and is located predominantly at position 1. InS. parasitica 20∶5n−3 is synthesized from 18∶3n−6via 20∶4n−6 and is located predominantly at position 2. It is suggested that the asymmetrical distribution of PUFA between positions 1 and 2 of glycerol Points towards different sites of synthesis of the two classes of PUFA, and that cross‐over between PUFA of the different types is prevented by thesn‐1 orsn‐2 positional specificity of the desaturases.

Fish again for dinner! The role of fish and other dietary oils in the therapy of skin disease

Adequate levels of polyunsaturated fatty acids are necessary for the normal functioning of most mammalian cells, both to provide fluidity to the cell membrane lipid bilayer and to function as precursors for the synthesis of the regulatory eicosanoids, prostaglandins, and leukotrienes. The omega-6 class of polyunsaturated fatty acids, such as linoleic and arachidonic acids, are of special importance as precursors for eicosanoid synthesis. The skin is a particularly good organ in which to study the effects of polyunsaturated fatty acids metabolism, inasmuch as either deficiencies of specific PUFA or overproduction of polyunsaturated fatty acids—derived prostaglandin and leukotriene result in specific, clinically recognizable cutaneous diseases. To help understand the pathogenesis of these diseases, polyunsaturated fatty acids metabolism is reviewed here, with emphasis on clinical manifestations of both deficiency syndromes and overproduction of proinflammatory eicosanoids. A rationale is presented for a therapeutic approach to inflammatory disease by dietary manipulation and substitution of omega-6 fatty acids by the unique omega- 3 class of polyunsaturated fatty acids found in fish. Evidence for the efficacy of fish oil in the therapy of specific inflammatory diseases is reviewed, as are the caveats regarding its therapeutic use. Dietary manipulations, specifically fish oil additives, appear to hold promise as therapeutic tools for cutaneous diseases.