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Frontiers in Immunology 2020Resolvins, the member of specialized pro-resolving mediators, are produced from omega-3 polyunsaturated fatty acids as a response to an acute inflammatory process in... (Review)
Review
Resolvins, the member of specialized pro-resolving mediators, are produced from omega-3 polyunsaturated fatty acids as a response to an acute inflammatory process in that termination and resolution of inflammation. In the acute inflammation, these lipid mediators limit polymorphonuclear cells infiltration, proinflammatory cytokine production; promote efferocytosis, and regulate several cell types being important roles in innate and adaptive immunity. Any dysregulation or defect of the resolution phase result in prolonged, persistent inflammation and eventually fibrosis. Resolvins are implicated in the development of various chronic autoimmune diseases. Systemic sclerosis (SSc) is a very complicated, chronic autoimmune disorder proceeding with vasculopathy, inflammation, and fibrosis. Dysregulation of innate and adaptive immunity is another important contributing factor in the pathogenesis of SSc. In this review, we will focus on the different roles of this new family of lipid mediators, characterized by the ability to prevent the spread of inflammation and its chronicity in various ways and how they can control the development of fibrotic diseases like SSc.
Topics: Animals; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Inflammation Mediators; Scleroderma, Systemic
PubMed: 32636845
DOI: 10.3389/fimmu.2020.01249 -
International Journal of Molecular... May 2022Fatty acids (FAs) are essential components of the central nervous system (CNS), where they exert multiple roles in health and disease. Among the FAs, docosahexaenoic... (Review)
Review
Fatty acids (FAs) are essential components of the central nervous system (CNS), where they exert multiple roles in health and disease. Among the FAs, docosahexaenoic acid (DHA) has been widely recognized as a key molecule for neuronal function and cell signaling. Despite its relevance, the molecular pathways underlying the beneficial effects of DHA on the cells of the CNS are still unclear. Here, we summarize and discuss the molecular mechanisms underlying the actions of DHA in neural cells with a special focus on processes of survival, morphological development, and synaptic maturation. In addition, we examine the evidence supporting a potential therapeutic role of DHA against CNS tumor diseases and tumorigenesis. The current results suggest that DHA exerts its actions on neural cells mainly through the modulation of signaling cascades involving the activation of diverse types of receptors. In addition, we found evidence connecting brain DHA and ω-3 PUFA levels with CNS diseases, such as depression, autism spectrum disorders, obesity, and neurodegenerative diseases. In the context of cancer, the existing data have shown that DHA exerts positive actions as a coadjuvant in antitumoral therapy. Although many questions in the field remain only partially resolved, we hope that future research may soon define specific pathways and receptor systems involved in the beneficial effects of DHA in cells of the CNS, opening new avenues for innovative therapeutic strategies for CNS diseases.
Topics: Brain; Central Nervous System; Central Nervous System Diseases; Docosahexaenoic Acids; Fatty Acids; Fatty Acids, Omega-3; Humans
PubMed: 35628201
DOI: 10.3390/ijms23105390 -
Cells Jul 2023The human lifespan has increased over the past century; however, healthspans have not kept up with this trend, especially cognitive health. Among nutrients for brain...
The human lifespan has increased over the past century; however, healthspans have not kept up with this trend, especially cognitive health. Among nutrients for brain function maintenance, long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFA): DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) must be highlighted, particularly structured forms of EPA and DHA which were developed to improve bioavailability and bioactivity in comparison with conventional ω-3 supplements. This study aims to elucidate the effect of a structured triglyceride form of DHA (DHA-TG) on the healthspan of aged . Using a thrashing assay, the nematodes were monitored at 4, 8, and 12 days of adulthood, and DHA-TG improved its motility at every age without affecting lifespan. In addition, the treatment promoted antioxidant capacity by enhancing the activity and expression of SOD (superoxide dismutase) in the nematodes. Lastly, as the effect of DHA-TG was lost in the DAF-16 mutant strain, it might be hypothesized that the effects of DHA need DAF-16/FOXO as an intermediary. In brief, DHA-TG exerted a healthspan-promoting effect resulting in both enhanced physical fitness and increased antioxidant defense in aged . For the first time, an improvement in locomotive function in aged wild-type nematodes is described following DHA-TG treatment.
Topics: Humans; Animals; Adult; Aged; Docosahexaenoic Acids; Antioxidants; Caenorhabditis elegans; Fatty Acids, Omega-3; Triglycerides
PubMed: 37566010
DOI: 10.3390/cells12151932 -
International Journal of Geriatric... May 2022Several recent clinical trials have shown that docosahexaenoic acid (DHA) supplements have a significant effect on cognition in cognitively impaired older adults. This... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Several recent clinical trials have shown that docosahexaenoic acid (DHA) supplements have a significant effect on cognition in cognitively impaired older adults. This randomised controlled trial aimed to investigate the cognitive effects of a DHA fish oil supplement in older adults with mild cognitive impairment, and to examine the moderating effect of the apolipoprotein E (APOE) ɛ4 allele on cognition and well-being.
METHODS/DESIGN
Seventy-two older adults between the ages of 60 and 90 from New Zealand were given a DHA supplement equivalent to 1491 mg DHA + 351 mg eicosapentaenoic acid per day or a placebo for a period of 12 months. Outcome measures included cognition, wellbeing and self-rated quality of life as well as height, weight, blood pressure and APOE genotyping.
RESULTS
The final analysis (n = 60) found no evidence of a treatment effect on cognitive measures, although did find a treatment effect on systolic blood pressure (p = 0.03, ƞ = 0.08), and a treatment interaction for APOE ɛ4 carriers on depression (p = 0.04, ƞ = 0.07) and anxiety (p = 0.02, ƞ = 0.09) scores in favour of the DHA supplement.
CONCLUSIONS
Despite no effect on cognition, the positive result in APOE ɛ4 carriers on depression and anxiety scores and on systolic blood pressure justifies further DHA trials. It may be a prudent step going forward for more studies to replicate the design elements (dose, duration and cognitive measures) of previous DHA trials to help understand why not all older adults appear to benefit from taking a fish oil supplement.
Topics: Aged; Cognition; Cognitive Dysfunction; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Humans; Quality of Life
PubMed: 35373862
DOI: 10.1002/gps.5707 -
The Journal of Biological Chemistry Jan 2023Astrocytic excitatory amino acid transporter 2 (EAAT2) plays a major role in removing the excitatory neurotransmitter L-glutamate (L-Glu) from synaptic clefts in the...
Astrocytic excitatory amino acid transporter 2 (EAAT2) plays a major role in removing the excitatory neurotransmitter L-glutamate (L-Glu) from synaptic clefts in the forebrain to prevent excitotoxicity. Polyunsaturated fatty acids such as docosahexaenoic acid (DHA, 22:6 n-3) enhance synaptic transmission, and their target molecules include EAATs. Here, we aimed to investigate the effect of DHA on EAAT2 and identify the key amino acid for DHA/EAAT2 interaction by electrophysiological recording of L-Glu-induced current in Xenopus oocytes transfected with EAATs, their chimeras, and single mutants. DHA transiently increased the amplitude of EAAT2 but tended to decrease that of excitatory amino acid transporter subtype 1 (EAAT1), another astrocytic EAAT. Single mutation of leucine (Leu) 434 to alanine (Ala) completely suppressed the augmentation by DHA, while mutation of EAAT1 Ala 435 (corresponding to EAAT2 Leu434) to Leu changed the effect from suppression to augmentation. Other polyunsaturated fatty acids (docosapentaenoic acid, eicosapentaenoic acid, arachidonic acid, and α-linolenic acid) similarly augmented the EAAT2 current and suppressed the EAAT1 current. Finally, our docking analysis suggested the most stable docking site is the lipid crevice of EAAT2, in close proximity to the L-Glu and sodium binding sites, suggesting that the DHA/Leu434 interaction might affect the elevator-like slide and/or the shapes of the other binding sites. Collectively, our results highlight a key molecular detail in the DHA-induced regulation of synaptic transmission involving EAATs.
Topics: Docosahexaenoic Acids; Excitatory Amino Acid Transporter 2; Glutamic Acid; Leucine; Synaptic Transmission; Mutation; Xenopus laevis
PubMed: 36509140
DOI: 10.1016/j.jbc.2022.102793 -
Arteriosclerosis, Thrombosis, and... Jan 2024Both cardiovascular disease (CVD) and cognitive decline are common features of aging. One in 5 deaths is cardiac for both men and women in the United States, and an... (Review)
Review
Both cardiovascular disease (CVD) and cognitive decline are common features of aging. One in 5 deaths is cardiac for both men and women in the United States, and an estimated 50 million are currently living with dementia worldwide. In this review, we summarize sex and racial differences in the role of fish and its very long chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in preventing CVD events and cognitive decline. In prospective studies, women with higher nonfried and fatty fish intake and women and Black individuals with higher plasma levels of EPA and DHA had a lower risk of CVD. In randomized controlled trials of EPA and DHA supplementation in primary CVD prevention, Black subjects benefited in a secondary outcome. In secondary CVD prevention, both men and women benefited, and Asians benefited as a prespecified subgroup. Fish and omega-3 polyunsaturated fatty acids are associated with prevention of cognitive decline in prospective studies. In randomized controlled trials of EPA and DHA supplementation, women have cognitive benefit. DHA seems more beneficial than EPA, and supplementation is more beneficial when started before cognitive decline. Although studies in women and racial groups are limited, life-long intake of nonfried and fatty fish lowers the risk of CVD and cognitive decline, and randomized controlled trials also show the benefit of EPA and DHA supplementation. These findings should be factored into recommendations for future research and clinical recommendations as dietary modalities could be cost-effective for disease prevention.
Topics: Male; Animals; Female; Humans; Fatty Acids, Omega-3; Prospective Studies; Race Factors; Dietary Supplements; Eicosapentaenoic Acid; Docosahexaenoic Acids; Cardiovascular Diseases; Cognition
PubMed: 37916414
DOI: 10.1161/ATVBAHA.122.318125 -
Nutricion Hospitalaria Aug 2023Docosahexaenoic acid (DHA) is a polyunsaturated essential fatty acid from the omega-3 series that appears to be key to perinatal mental health. For this, the aim of this... (Review)
Review
Docosahexaenoic acid (DHA) is a polyunsaturated essential fatty acid from the omega-3 series that appears to be key to perinatal mental health. For this, the aim of this review is to evaluate the effect of DHA on maternal mental health during pregnancy and lactation with respect to depression and anxiety. The present scoping review was carried out following the methodology of Arksey and O'Malley (2005). The selection of studies was carried out in accordance with PRISMA by means of systematic searches in the PubMed, Scopus, PsycINFO and Medline databases. The results classified according to the effectiveness of DHA. In most (n = 9) of the 14 studies finally included, DHA plasma levels with or without other polyunsaturated omega-3 fatty acids were significantly lower in pregnant women with depressive and anxiety symptoms. However, no study reported a beneficial effect of DHA on mental health during the postpartum period. The majority used detection method was the Edinburgh Postpartum Depression Scale (n = 11). The prevalence of depressive symptoms ranged between 5.9 % and 50 %. As a conclusion, although more research is needed in this area, these exploratory results suggest that DHA could play an important role in preventing the pathogenesis of depression and anxiety during gestation.
Topics: Pregnancy; Female; Humans; Docosahexaenoic Acids; Mental Health; Fatty Acids, Omega-3; Postpartum Period; Lactation
PubMed: 37334807
DOI: 10.20960/nh.04523 -
Clinical Nutrition (Edinburgh, Scotland) May 2024Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIM
Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine associations between DHA, AA, and inflammation-related proteins during the neonatal period in extremely preterm infants.
METHODS
A retrospective exploratory study of infants (n = 183) born below 28 weeks gestation from the Mega Donna Mega trial, a randomized multicenter trial designed to study the effect of DHA and AA on retinopathy of prematurity. Serial serum samples were collected after birth until postnatal day 100 (median 7 samples per infant) and analyzed for phospholipid fatty acids and proteins using targeted proteomics covering 538 proteins. Associations over time between LCPUFAs and proteins were explored using mixed effect modeling with splines, including an interaction term for time, and adjusted for gestational age, sex, and center.
RESULTS
On postnatal day one, 55 proteins correlated with DHA levels and 10 proteins with AA levels. Five proteins were related to both fatty acids, all with a positive correlation. Over the first 100 days after birth, we identified 57 proteins to be associated with DHA and/or AA. Of these proteins, 41 (72%) related to inflammation. Thirty-eight proteins were associated with both fatty acids and the overall direction of association did not differ between DHA and AA, indicating that both LCPUFAs similarly contribute to up- and down-regulation of the preterm neonate inflammatory proteome. Primary examples of this were the inflammation-modulating cytokines IL-6 and CCL7, both being negatively related to levels of DHA and AA in the postnatal period.
CONCLUSIONS
This study supports postnatal non-antagonistic and potentially synergistic effects of DHA and AA on the inflammation proteome in preterm infants, indicating that supplementation with both fatty acids may contribute to limiting the disease burden in this vulnerable population.
CLINICAL REGISTRATION NUMBER
ClinicalTrials.gov (NCT03201588).
Topics: Humans; Docosahexaenoic Acids; Arachidonic Acid; Infant, Extremely Premature; Infant, Newborn; Female; Retrospective Studies; Male; Inflammation; Proteome
PubMed: 38603973
DOI: 10.1016/j.clnu.2024.03.031 -
Nutrients Jul 2023Docosahexaenoic acid (C22:6-3, DHA) is the precursor of specialized pro-resolving lipid mediators (SPMs), such as resolvin, protectin, and maresin families which have... (Review)
Review
Docosahexaenoic acid (C22:6-3, DHA) is the precursor of specialized pro-resolving lipid mediators (SPMs), such as resolvin, protectin, and maresin families which have been considered therapeutic bioactive compounds for human health. Growing evidence indicates that DHA and SPMs are beneficial strategies in the amelioration, regulation, and duration of inflammatory processes through different biological actions. The present review discusses the reported therapeutic benefits of SPMs on various diseases and their potential clinical applications.
Topics: Humans; Docosahexaenoic Acids; Eicosanoids; Inflammation; Inflammation Mediators
PubMed: 37571256
DOI: 10.3390/nu15153317 -
Journal of Neurochemistry May 2023Dietary lipids, particularly omega-3 polyunsaturated fatty acids, are speculated to impact behaviors linked to the dopaminergic system, such as movement and control of...
Dietary lipids, particularly omega-3 polyunsaturated fatty acids, are speculated to impact behaviors linked to the dopaminergic system, such as movement and control of circadian rhythms. However, the ability to draw a direct link between dopaminergic omega-3 fatty acid metabolism and behavioral outcomes has been limited to the use of diet-based approaches, which are confounded by systemic effects. Here, neuronal lipid metabolism was targeted in a diet-independent manner by manipulation of long-chain acyl-CoA synthetase 6 (ACSL6) expression. ACSL6 performs the initial reaction for cellular fatty acid metabolism and prefers the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA). The loss of Acsl6 in mice (Acsl6 ) depletes neuronal membranes of DHA content and results in phenotypes linked to dopaminergic control, such as hyperlocomotion, impaired short-term spatial memory, and imbalances in dopamine neurochemistry. To investigate the role of dopaminergic ACSL6 on these outcomes, a dopaminergic neuron-specific ACSL6 knockout mouse was generated (Acsl6 ). Acsl6 mice demonstrated hyperlocomotion and imbalances in striatal dopamine neurochemistry. Circadian rhythms of both the Acsl6 and the Acsl6 mice were similar to control mice under basal conditions. However, upon light entrainment, a mimetic of jet lag, both the complete knockout of ACSL6 and the dopaminergic-neuron-specific loss of ACSL6 resulted in a longer recovery to entrainment compared to control mice. In conclusion, these data demonstrate that ACSL6 in dopaminergic neurons alters dopamine metabolism and regulation of light entrainment suggesting that DHA metabolism mediated by ACSL6 plays a role in dopamine neuron biology.
Topics: Mice; Animals; Dopaminergic Neurons; Lipid Metabolism; Dopamine; Dietary Fats; Diet; Mice, Knockout; Docosahexaenoic Acids; Coenzyme A Ligases
PubMed: 36815399
DOI: 10.1111/jnc.15793