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Advances in Nutrition (Bethesda, Md.) Nov 2016
Topics: Diet; Dietary Supplements; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Evidence-Based Medicine; Humans; Meta-Analysis as Topic; Observational Studies as Topic; Randomized Controlled Trials as Topic; Recommended Dietary Allowances
PubMed: 28140331
DOI: 10.3945/an.116.012963 -
International Journal of Molecular... Jan 2022Inflammation is an essential action to protect the host human body from external, harmful antigens and microorganisms. However, an excessive inflammation reaction... (Review)
Review
Inflammation is an essential action to protect the host human body from external, harmful antigens and microorganisms. However, an excessive inflammation reaction sometimes exceeds tissue damage and can disrupt organ functions. Therefore, anti-inflammatory action and resolution mechanisms need to be clarified. Dietary foods are an essential daily lifestyle that influences various human physiological processes and pathological conditions. Especially, omega-3 fatty acids in the diet ameliorate chronic inflammatory skin diseases. Recent studies have identified that omega-3 fatty acid derivatives, such as the resolvin series, showed strong anti-inflammatory actions in various inflammatory diseases. Maresin-1 is a derivative of one of the representative omega-3 fatty acids, i.e., docosahexaenoic acid (DHA), and has shown beneficial action in inflammatory disease models. In this review, we summarize the detailed actions of maresin-1 in immune cells and inflammatory diseases.
Topics: Anti-Inflammatory Agents; Diet; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; Inflammation
PubMed: 35163291
DOI: 10.3390/ijms23031367 -
Nutrients Feb 2016Docosahexaenoic acid (DHA) is the predominant omega-3 (n-3) polyunsaturated fatty acid (PUFA) found in the brain and can affect neurological function by modulating... (Review)
Review
Docosahexaenoic acid (DHA) is the predominant omega-3 (n-3) polyunsaturated fatty acid (PUFA) found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action.
Topics: Aging; Brain; Cognition; Docosahexaenoic Acids; Humans
PubMed: 26901223
DOI: 10.3390/nu8020099 -
International Journal of Molecular... Apr 2022The neurodevelopmental and neuroprotective actions of docosahexaenoic acid (DHA) are mediated by mechanisms involving membrane- and metabolite-related signal... (Review)
Review
The neurodevelopmental and neuroprotective actions of docosahexaenoic acid (DHA) are mediated by mechanisms involving membrane- and metabolite-related signal transduction. A key characteristic in the membrane-mediated action of DHA results from the stimulated synthesis of neuronal phosphatidylserine (PS). The resulting DHA-PS-rich membrane domains facilitate the translocation and activation of kinases such as Raf-1, protein kinase C (PKC), and Akt. The activation of these signaling pathways promotes neuronal development and survival. DHA is also metabolized in neural tissues to bioactive mediators. Neuroprotectin D1, a docosatriene synthesized by the lipoxygenase activity, has an anti-inflammatory property, and elovanoids formed from DHA elongation products exhibit antioxidant effects in the retina. Synaptamide, an endocannabinoid-like lipid mediator synthesized from DHA in the brain, promotes neurogenesis and synaptogenesis and exerts anti-inflammatory effects. It binds to the GAIN domain of the GPR110 (ADGRF1) receptor, triggers the cAMP/protein kinase A (PKA) signaling pathway, and activates the cAMP-response element binding protein (CREB). The DHA status in the brain influences not only the PS-dependent signal transduction but also the metabolite formation and expression of pre- and post-synaptic proteins that are downstream of the CREB and affect neurotransmission. The combined actions of these processes contribute to the neurodevelopmental and neuroprotective effects of DHA.
Topics: Anti-Inflammatory Agents; Cyclic AMP Response Element-Binding Protein; Docosahexaenoic Acids; Endocannabinoids; Neuroprotection; Signal Transduction
PubMed: 35563025
DOI: 10.3390/ijms23094635 -
FEBS Letters Sep 2017Omega-3 (ω-3) fatty acids (FAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are known to have important roles in human health and disease.... (Review)
Review
Omega-3 (ω-3) fatty acids (FAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are known to have important roles in human health and disease. Besides being utilized as fuel, ω-3 FAs have specific functions based on their structural characteristics. These functions include serving as ligands for several receptors, precursors of lipid mediators, and components of membrane glycerophospholipids (GPLs). Since ω-3 FAs (especially DHA) are highly flexible, the levels of DHA in GPLs may affect membrane biophysical properties such as fluidity, flexibility, and thickness. Here, we summarize some of the cellular mechanisms for incorporating DHA into membrane GPLs and propose biological effects and functions of DHA-containing membranes of several cell and tissue types.
Topics: Cell Membrane; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Glycerophospholipids; Membrane Fluidity; Models, Biological
PubMed: 28833063
DOI: 10.1002/1873-3468.12825 -
International Journal of Molecular... Aug 2016The human diet contains low amounts of ω-3 polyunsaturated fatty acids (PUFAs) and high amounts of ω-6 PUFAs, which has been reported to contribute to the incidence of... (Review)
Review
The human diet contains low amounts of ω-3 polyunsaturated fatty acids (PUFAs) and high amounts of ω-6 PUFAs, which has been reported to contribute to the incidence of cancer. Epidemiological studies have shown that a high consumption of fish oil or ω-3 PUFAs reduced the risk of colon, pancreatic, and endometrial cancers. The ω-3 PUFA, docosahexaenoic acid (DHA), shows anticancer activity by inducing apoptosis of some human cancer cells without toxicity against normal cells. DHA induces oxidative stress and oxidative DNA adduct formation by depleting intracellular glutathione (GSH) and decreasing the mitochondrial function of cancer cells. Oxidative DNA damage and DNA strand breaks activate DNA damage responses to repair the damaged DNA. However, excessive DNA damage beyond the capacity of the DNA repair processes may initiate apoptotic signaling pathways and cell cycle arrest in cancer cells. DHA shows a variable inhibitory effect on cancer cell growth depending on the cells' molecular properties and degree of malignancy. It has been shown to affect DNA repair processes including DNA-dependent protein kinases and mismatch repair in cancer cells. Moreover, DHA enhanced the efficacy of anticancer drugs by increasing drug uptake and suppressing survival pathways in cancer cells. In this review, DHA-induced oxidative DNA damage, apoptotic signaling, and enhancement of chemosensitivity in cancer cells will be discussed based on recent studies.
Topics: Animals; Antineoplastic Agents; Apoptosis; DNA Damage; Docosahexaenoic Acids; Drug Resistance, Neoplasm; Humans; Neoplasms; Oxidative Stress
PubMed: 27527148
DOI: 10.3390/ijms17081257 -
Lipids in Health and Disease Jun 2017Docosahexaenoic acid (DHA) is present in high concentrations in salmon, herring, and trout. Epidemiologic studies have shown that high dietary consumption of these and... (Review)
Review
Docosahexaenoic acid (DHA) is present in high concentrations in salmon, herring, and trout. Epidemiologic studies have shown that high dietary consumption of these and other oily fish is associated with reduced rates of myocardial infarction, atherosclerosis, and other ischemic pathologies. Atherosclerosis is induced by inflammation and can lead to acute cardiovascular events and extensive plaque. DHA inhibits the development of inflammation in endothelial cells, alters the function and regulation of vascular biomarkers, and reduces cardiovascular risk. It also affects vascular relaxation and constriction by controlling nitric oxide and endothelin 1 production in endothelial cells. DHA also contributes to the prevention of arteriosclerosis by regulating the expression of oxidized low density lipoprotein receptor 1, plasminogen activator inhibitor 1, thromboxane A2 receptor, and adhesion molecules such as vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and intercellular adhesion molecule 1 in endothelial cells. Recent research showed that DHA reduces the increase in adhesion factor expression induced by lipopolysaccharide by suppressing toll-like receptor 4. A new mechanism of action of DHA has been described that is mediated through endothelial free fatty acid receptor 4, associated with heme oxygenase 1 induction by Nrf2. However, the efficacy and mechanisms of action of DHA in cardiovascular disease prevention are not yet completely understood. The aim of this paper was to review the effects of DHA on vascular endothelial cells and recent findings on their potential for the prevention of circulatory diseases.
Topics: Animals; Cardiovascular Diseases; Docosahexaenoic Acids; Endothelial Cells; Humans; Risk Factors; Toll-Like Receptor 4
PubMed: 28619112
DOI: 10.1186/s12944-017-0514-6 -
Applied and Environmental Microbiology Mar 2022The heterotrophic marine microalgae sp. is an important industrial producer of docosahexaenoic acid (DHA). Increased production of DHA and lipids in sp. has been...
The heterotrophic marine microalgae sp. is an important industrial producer of docosahexaenoic acid (DHA). Increased production of DHA and lipids in sp. has been achieved by standard fermentation optimization and metabolic engineering methods; however, regulatory mechanisms for DHA and lipid biosynthesis remain unknown. In this study, the CH zinc finger protein LipR was identified in sp. ATCC 20888 by transcriptional analysis. Deletion of the gene significantly (0.001) increased production of total lipids and DHA by 33% and 48%, respectively. LipR repressed DHA and lipid production by directly inhibiting transcription of polyunsaturated fatty acid (PUFA) and fatty acid synthase (FAS) genes (, , , and ). Specific binding of LipR to 9-bp recognition sequence 5'-(C/A)(A/G)CCATCTT-3' in upstream regions of target genes was demonstrated by electrophoretic mobility shift assays (EMSAs) and DNase I footprinting assays. Expression of several key genes (, , , , , , and ) related to levels of precursors and NADPH, and to triacylglycerol storage rate, were also directly repressed by LipR. Our findings, taken together, indicate that the evolutionarily unique regulator LipR is an essential repressor of DHA and saturated fatty acid biosynthesis in sp. Regulatory mechanisms for DHA and saturated fatty acid biosynthesis in the heterotrophic marine microalgae sp. are unclear. We demonstrate here that deletion of the gene () encoding the CH zinc finger protein LipR promotes DHA and saturated fatty acid production in this genus. LipR acts as a key repressor of such production by binding to 9-bp consensus sequence 5'-(C/A)(A/G)CCATCTT-3' in the upstream regions of polyunsaturated fatty acid and fatty acid synthase genes (, , , and ), and genes related to levels of precursors and NADPH (, , , , , and ), and to triacylglycerol storage rate (). This is the first demonstration that a regulator inhibits synthesis of DHA and lipids in sp. by directly controlling transcription of PUFA synthase and genes. Manipulation of the gene provides a potential strategy for enhancing accumulation of polyunsaturated fatty acids and lipids in thraustochytrids.
Topics: Docosahexaenoic Acids; Fatty Acids; Fatty Acids, Unsaturated; Stramenopiles; Zinc Fingers
PubMed: 35108079
DOI: 10.1128/aem.02063-21 -
Seminars in Immunology Jan 2022Specialized pro-resolving mediators (SPMs) are endogenous small molecules produced mainly from dietary omega-3 polyunsaturated fatty acids by both structural cells and... (Review)
Review
Specialized pro-resolving mediators (SPMs) are endogenous small molecules produced mainly from dietary omega-3 polyunsaturated fatty acids by both structural cells and cells of the active and innate immune systems. Specialized pro-resolving mediators have been shown to both limit acute inflammation and promote resolution and return to homeostasis following infection or injury. There is growing evidence that chronic immune disorders are characterized by deficiencies in resolution and SPMs have significant potential as novel therapeutics to prevent and treat chronic inflammation and immune system disorders. This review focuses on important breakthroughs in understanding how SPMs are produced by, and act on, cells of the adaptive immune system, specifically macrophages, B cells and T cells. We also highlight recent evidence demonstrating the potential of SPMs as novel therapeutic agents in topics including immunization, autoimmune disease and transplantation.
Topics: Humans; Docosahexaenoic Acids; Fatty Acids, Omega-3; Inflammation; Inflammation Mediators; Immunity
PubMed: 35660338
DOI: 10.1016/j.smim.2022.101605 -
International Journal of Molecular... Mar 2023High-density lipoproteins (HDLs) are known to enhance vascular function through different mechanisms, including the delivery of functional lipids to endothelial cells....
High-density lipoproteins (HDLs) are known to enhance vascular function through different mechanisms, including the delivery of functional lipids to endothelial cells. Therefore, we hypothesized that omega-3 (n-3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content of HDLs would improve the beneficial vascular effects of these lipoproteins. To explore this hypothesis, we performed a placebo-controlled crossover clinical trial in 18 hypertriglyceridemic patients without clinical symptoms of coronary heart disease who received highly purified EPA 460 mg and DHA 380 mg, twice a day for 5 weeks or placebo. After 5 weeks of treatment, patients followed a 4-week washout period before crossover. HDLs were isolated using sequential ultracentrifugation for characterization and determination of fatty acid content. Our results showed that n-3 supplementation induced a significant decrease in body mass index, waist circumference as well as triglycerides and HDL-triglyceride plasma concentrations, whilst HDL-cholesterol and HDL-phospholipids significantly increased. On the other hand, HDL, EPA, and DHA content increased by 131% and 62%, respectively, whereas 3 omega-6 fatty acids significantly decreased in HDL structures. In addition, the EPA-to-arachidonic acid (AA) ratio increased more than twice within HDLs suggesting an improvement in their anti-inflammatory properties. All HDL-fatty acid modifications did not affect the size distribution or the stability of these lipoproteins and were concomitant with a significant increase in endothelial function assessed using a flow-mediated dilatation test (FMD) after n-3 supplementation. However, endothelial function was not improved in vitro using a model of rat aortic rings co-incubated with HDLs before or after treatment with n-3. These results suggest a beneficial effect of n-3 on endothelial function through a mechanism independent of HDL composition. In conclusion, we demonstrated that EPA and DHA supplementation for 5 weeks improved vascular function in hypertriglyceridemic patients, and induced enrichment of HDLs with EPA and DHA to the detriment of some n-6 fatty acids. The significant increase in the EPA-to-AA ratio in HDLs is indicative of a more anti-inflammatory profile of these lipoproteins.
Topics: Animals; Rats; Arachidonic Acid; Cross-Over Studies; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Endothelial Cells; Fatty Acids; Fatty Acids, Omega-3; Lipoproteins; Triglycerides; Humans
PubMed: 36982461
DOI: 10.3390/ijms24065390