linoleic-acid and eicosapentaenoic-acid-ethyl-ester

The health of the individual and the population in general is the result of interaction between genetics and various environmental factors, of which diet/nutrition is the most important. The focus of this paper is on the association of high n-6 PUFA or low n-3 PUFA due to genetic variation and/or dietary intake, with changes in specialized pro-resolving mediators (SPMs), cytokine storm, inflammation-resolution and Covid-19. Human beings evolved on a diet that was balanced in the n-6 and n-3 essential fatty acids with a ratio of n-6/n-3 of 1-2/1 whereas today this ratio is 16/1. Such a high ratio due to high amounts of n-6 fatty acids leads to a prothrombotic and proinflammatory state and is associated with obesity, diabetes, cardiovascular disease, and some forms of cancer. In addition to the high intake of n-6 fatty acids that increases inflammation there is genetic variation in the biosynthesis of n-6 linoleic acid (LA) to arachidonic acid (ARA) and of linolenic (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Present day humans have two common FADS haplotypes that differ dramatically in their ability to generate long-chain fatty acids. The more efficient, evolutionary derived haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and could have provided an advantage in environments with limited access to dietary long-chain fatty acids ARA, EPA and DHA. In the modern world this haplotype has been associated with lifestyle-related diseases, such as cardiovascular disease, obesity, diabetes, all of which are characterized by increased levels of inflammation. African Americans and Latino populations have increased susceptibility and higher death rates from SARS-CoV-2 than whites. These populations are characterized by increased numbers of persons (about 80%) that are fast metabolizers, leading to increased production of ARA, as well as poor intake of fruits and vegetables. The combinations of fast metabolism and high n-6 intake increases their inflammatory status and possibly susceptibility of SARS-CoV-2. In vitro and human studies indicate that the specialized pro-resolving mediators (SPM) produced from the n-3, EPA and DHA influence the resolution of inflammation, allowing the tissues to return to function and homeostasis. The SPMs each counter-regulate cytokine storms, as well as proinflammatory lipid mediators via NFκB and inflammasome down regulation and reduce the proinflammatory eicosa

Topics: COVID-19; Docosahexaenoic Acids; Eicosanoids; Eicosapentaenoic Acid; Fatty Acids, Essential; Fatty Acids, Omega-3; Genetic Predisposition to Disease; Haplotypes; Humans; Inflammation; Linoleic Acid; RNA, Viral; SARS-CoV-2

Polyunsaturated fatty acids (PUFAs) are essential for fetal development, and intrauterine transfer is the only supply of PUFAs to the fetus. The prevailing theory of gestational nutrient transfer is that certain nutrients (including PUFAs) may have prioritized transport across the placenta. Numerous studies have identified correlations between maternal and infant fatty acid concentrations; however, little is known about what role maternal PUFA status may play in differential intrauterine nutrient transfer. Twenty mother-infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood, and placental tissue samples. Plasma concentrations of PUFAs were assessed using gas chromatography (GC-FID). Intrauterine transfer percentages for each fatty acid were calculated as follows: ((cord blood fatty acid level/maternal blood fatty acid level) × 100). Kruskal-Wallis tests were used to compare transfer percentages between maternal fatty acid tertile groups. A

Topics: Arachidonic Acid; Cross-Sectional Studies; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Fetal Blood; Fetal Development; Fetus; Humans; Infant; Linoleic Acid; Male; Placenta; Pregnancy

The metabolic state of an organism instructs gene expression modalities, leading to changes in complex life history traits, such as longevity. Dietary restriction (DR), which positively affects health and life span across species, leads to metabolic reprogramming that enhances utilisation of fatty acids for energy generation. One direct consequence of this metabolic shift is the upregulation of cytoprotective (CyTP) genes categorized in the Gene Ontology (GO) term of "Xenobiotic Detoxification Program" (XDP). How an organism senses metabolic changes during nutritional stress to alter gene expression programs is less known. Here, using a genetic model of DR, we show that the levels of polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and eicosapentaenoic acid (EPA), are increased following DR and these PUFAs are able to activate the CyTP genes. This activation of CyTP genes is mediated by the conserved p38 mitogen-activated protein kinase (p38-MAPK) pathway. Consequently, genes of the PUFA biosynthesis and p38-MAPK pathway are required for multiple paradigms of DR-mediated longevity, suggesting conservation of mechanism. Thus, our study shows that PUFAs and p38-MAPK pathway function downstream of DR to help communicate the metabolic state of an organism to regulate expression of CyTP genes, ensuring extended life span.

Topics: Animals; Biochemical Phenomena; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Gene Expression Regulation; Gene Knockdown Techniques; Linoleic Acid; Longevity; Metabolic Networks and Pathways; p38 Mitogen-Activated Protein Kinases; Protein Serine-Threonine Kinases

Acrylamide (ACR), a ubiquitous agent, has various chemical and industrial applications, and it is found in backed or fried carbohydrate-rich food. It has been related to multiple toxicological effects, and it causes high cytotoxicity through oxidative stress. The present study aimed to investigate the potential effect of ACR toxicity administered at different concentrations (5, 10, and 20 mg/L), during 5 days, in order to evaluate the fatty acid (FA) composition and redox state in the digestive gland of Mactra corallina. The results showed, in ACR-treated clams, a significant increase in malondialdehyde, hydrogen peroxide, protein carbonyl, and metallothionein levels, as well as an alteration of the enzymatic (superoxide dismutase, glutathione peroxidase, and catalase) and non-enzymatic (reduced glutathione and ascorbic acid) antioxidant status. However, acetylcholinesterase activity was inhibited in a concentration-dependent manner. In our experiment, the n-3 (Omega-3) and n-6 (Omega-6) polyunsaturated fatty acid levels were significantly changed in all ACR-treated groups. A decrease in eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA) was observed in 10-mg/L and 20-mg/L ACR-treated groups. Nevertheless, arachidonic acid (C20:4n-6, ARA) and its precursor linoleic acid (C18:2n-6, LA) were increased. Besides oxidative stress parameters, FA composition may be an additional tool for assessing ACR contamination.

Topics: Acrylamide; Animals; Antioxidants; Arachidonic Acid; Bivalvia; Catalase; Digestion; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Glutathione; Linoleic Acid; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase

Neuro-active pharmaceuticals have been reported to act as endocrine disruptors enhancing reproduction in the model crustacean Daphnia manga at environmental concentrations of ng/L. Oxylipins and more specifically eicosanoids, which are lipid mediators formed from polyunsaturated fatty acids (PUFAs), are known to regulate reproduction together with other physiological processes in insects. In D. magna, the biosynthesis of eicosanoids and their putative role in the regulation of reproduction has been studied using transcriptomics, genomics and exposures to cyclooxygenase inhibitors. Quantification of eicosanoids and oxylipins derived from PUFAs upon exposure to pharmaceuticals is therefore crucial for a better understanding of the mode of action of neuro-active pharmaceuticals on aquatic invertebrates. The aim of this study was to investigate shifts in the oxylipin profile in D. magna adults upon exposure to environmental concentrations of the three psychiatric drugs, fluoxetine, diazepam and carbamazepine, with known effects of enhancing offspring production. Oxylipin profiles were determined in whole organism tissues using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Up to 28 different oxylipins belonging to arachidonic (AA), linoleic acid (LA), α-linoleic acid (α-LA) and eicosapentaenoic acid (EPA) pathways were detected and quantified in D. magna adults. Exposure to the selected psychiatric drugs showed that fluoxetine enhanced the accumulation of the cyclooxygenase (COX) product 12-hydroxyheptadecatrienoic acid (12-HHTrE), whereas diazepam increased the concentration of eicosanoids belonging to the lipoxygenase (LOX) and cytochrome P450 (CYP) pathways (HETEs, EpOMEs, HODEs, HOTrEs and HEPEs) from the AA, LA, αLA and EPA pathways. Carbamazepine had little effect and only one LA-derived compound from the LOX pathway (13-HODE) increased significantly. This means that despite having different modes of action in humans, fluoxetine and diazepam up-regulated eicosanoid pathways in D. magna, closely related to known biologically active products that regulate reproduction in insects.

Topics: Animals; Daphnia; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Linoleic Acid; Oxylipins; Psychotropic Drugs; Water Pollutants, Chemical

Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted from intestinal L-cells and now considered as an ideal diabetic medicine. Recently, it was reported that the unsaturated fatty acid alpha-linoleic acid promotes the secretion of GLP-1 via a G protein-coupled receptor, GPR120. However, the effects of long-chain polyunsaturated fatty acids on the secretion of GLP-1 have not been examined in vivo. The aim of this study was to evaluate the effects of the long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on blood glucose levels, plasma insulin, and GLP-1 concentrations. In addition, site-specific differences in these effects were determined using several intestinal segments: stomach, jejunum, and colon. After an intraperitoneal glucose administration (1.5 mg/g weight), each mouse was administered vehicle or an alpha-linoleic acid, DHA, EPA or EPA ester (EPA-E) solution to each intestinal segment. After an intraperitoneal glucose challenge, marked endogenous GLP-1 secretion, substantial insulin release and subsequent glucose reductions were observed in the intracolonic DHA and EPA treatment groups. In contrast, DHA and EPA did not increase GLP-1 secretion when given in the other segments. These data suggested that the colon-specific delivery of DHA, EPA, and possibly EPA-E would be a novel antidiabetic treatment by the stimulation of intrinsic GLP-1 secretion.

Topics: Animals; Blood Glucose; Colon; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Eicosapentaenoic Acid; Gastric Mucosa; Glucagon-Like Peptide 1; Hypoglycemic Agents; Insulin; Jejunum; Linoleic Acid; Male; Mice; Mice, Inbred Strains; Stomach

The fatty acid composition of rat polymorphonuclear leukocytes (PMN) was modified by diets supplemented with a high linoleate (LA) safflower oil (76% LA), mixtures of eicosapentaenoate (EPA) and safflower oil (EPA(20) containing 20% EPA and 61% LA, EPA(40) containing 40% EPA and 46% LA), mixtures of docosahexaenoate (DHA) and safflower oil (DHA(20) containing 20% DHA and 61% LA, DHA(40) containing 40% DHA and 46% LA) or a high alpha-linolenate (alpha-LNA) perilla oil (57% alpha-LNA and 13% LA), and then lipid mediator production in casein-induced peritoneal PMN were compared. EPA and DHA were relatively ineffective in reducing platelet-activating factor (PAF) production; a statistically significant reduction was observed only in the DHA(40) group. In contrast, perilla oil reduced PAF production by 50% as compared with safflower oil. Arachidonate (AA) in the PAF precursor, 1-alkyl-2-acyl-glycerophosphocholine, was roughly correlated with PAF production, but EPA and DHA in the precursor lipid were relatively unrelated. On the other hand, both PGE2 and LTB4 production correlated positively with AA and negatively with EPA and DHA in PMN phospholipids; EPA tended to be somewhat more effective than DHA in reducing PGE2 and LTB4 formation; the activity of perilla oil was no less than EPA(20). Thus, replacing safflower oil with perilla oil was no less effective than supplementing safflower oil with EPA or DHA (at 40% of total fatty acids) in reducing lipid mediator production in rat PMN.

Topics: alpha-Linolenic Acid; Animals; Calcimycin; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Eicosanoids; Eicosapentaenoic Acid; Ionophores; Linoleic Acid; Male; Neutrophils; Phospholipids; Plant Oils; Platelet Activating Factor; Rats; Rats, Sprague-Dawley; Safflower Oil