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Comprehensive Reviews in Food Science... Jul 2020In recent years, docosahexaenoic acid-containing phospholipids (DHA-PLs) have attracted much attention because of theirs unique health benefits. Compared with other... (Review)
Review
In recent years, docosahexaenoic acid-containing phospholipids (DHA-PLs) have attracted much attention because of theirs unique health benefits. Compared with other forms of docosahexaenoic acid (DHA), DHA-PLs possess superior biological effects (e.g., anticancer, lipid metabolism regulation, visual development, and brain and nervous system biochemical reactions), more intricate metabolism mechanisms, and a stronger attraction to consumer. The production of DHA-PLs is hampered by several challenges associated with the limited content of DHA-PLs in natural sources, incomplete utilization of by-products, few microorganisms for DHA-PLs production, high cost, and complex process of artificial preparation of DHA-PLs. In this article, the sources, biological activities, and commercial applications of DHA-PLs were summarized, with intensive discussions on advantages of DHA-PLs over DHA, isomerism of DHA in phospholipids (PLs), and brain health. The excellent biological characteristics of DHA-PLs are primarily concerned with DHA and PLs. The metabolic fate of different DHA-PLs varies from the position of DHA in PLs to polar groups in DHA-PLs. Overall, well understanding of DHA-PLs about their sources and characteristics is critical to accelerate the production of DHA-PLs, economically enhance the value of DHA-PLs, and improve the applicability of DHA-PLs and the acceptance of consumers.
Topics: Brain; Docosahexaenoic Acids; Humans; Isomerism; Phospholipids
PubMed: 33337094
DOI: 10.1111/1541-4337.12543 -
Nutrition Reviews May 2016Recently, the European Food Safety Authority asserted that arachidonic acid (ARA) is an optional nutrient for the term infant even when docosahexaenoic acid (DHA) is... (Review)
Review
Recently, the European Food Safety Authority asserted that arachidonic acid (ARA) is an optional nutrient for the term infant even when docosahexaenoic acid (DHA) is present. The brief rationale is based on an explicit, widespread misapplication of the concept of "essential fatty acids" to linoleic acid that implies it is uniquely required as a nutrient per se. Linoleic acid prevents acute clinical symptoms caused by polyunsaturated fatty acid-deficient diets and is the major precursor for ARA in most human diets. Experimental diets with ARA as the sole n-6 similarly prevent symptoms but at a lower energy percentage than linoleic acid and show ARA is a precursor for linoleic acid. The absence of consistent evidence of ARA benefit from randomized controlled trials is apparently an issue as well. This review highlights basic and clinical research relevant to ARA requirements as an adjunct to DHA in infancy. ARA is a major structural central nervous system component, where it rapidly accumulates perinatally and is required for signaling. Tracer studies show that ARA-fed infants derive about half of their total body ARA from dietary preformed ARA. Clinically, of the 3 cohorts of term infants studied with designs isolating the effects of ARA (DHA-only vs DHA+ARA), none considered ARA-specific outcomes such as vascular or immune function; the study with the highest ARA level showed significant neurocognitive benefit. All breastfed term infants of adequately nourished mothers consume both DHA and ARA. The burden of proof to substantially deviate from the composition of breastmilk is greater than that available from inherently empirical human randomized controlled trial evidence. Infant formulas with DHA but without ARA risk harm from suppression of ARA-mediated metabolism manifest among the many unstudied functions of ARA.
Topics: Arachidonic Acid; Dietary Fats; Docosahexaenoic Acids; Fatty Acids, Essential; Humans; Infant; Infant Formula; Linoleic Acid; Milk, Human; Nutritional Requirements
PubMed: 27013482
DOI: 10.1093/nutrit/nuw007 -
Marine Drugs Aug 2023Epilepsy is a chronic neurological disorder that is more prevalent in children, and recurrent unprovoked seizures can lead to cognitive impairment. Numerous studies have...
Epilepsy is a chronic neurological disorder that is more prevalent in children, and recurrent unprovoked seizures can lead to cognitive impairment. Numerous studies have reported the benefits of docosahexaenoic acid (DHA) on neurodevelopment and cognitive ability, while comparatively less attention has been given to eicosapentaenoic acid (EPA). Additionally, little is known about the effects and mechanisms of DHA and EPA in relation to seizure-induced cognitive impairment in the young rodent model. Current research indicates that ferroptosis is involved in epilepsy and cognitive deficiency in children. Further investigation is warranted to determine whether EPA or DHA can mitigate seizure-induced cognitive deficits by inhibiting ferroptosis. Therefore, this study was conducted to compare the effects of DHA and EPA on seizure-induced cognitive deficiency and reveal the underlying mechanisms focused on ferroptosis in a pentylenetetrazol (PTZ)-kindling young mice model. Mice were fed a diet containing DHA-enriched ethyl esters or EPA-enriched ethyl esters for 21 days at the age of 3 weeks and treated with PTZ (35 mg/kg, i.p.) every other day 10 times. The findings indicated that both EPA and DHA exhibited ameliorative effects on seizure-induced cognitive impairment, with EPA demonstrating a superior efficacy. Further mechanism study revealed that supplementation of DHA and EPA significantly increased cerebral DHA and EPA levels, balanced neurotransmitters, and inhibited ferroptosis by modulating iron homeostasis and reducing lipid peroxide accumulation in the hippocampus through activating the Nrf2/Sirt3 signal pathway. Notably, EPA exhibited better an advantage in ameliorating iron dyshomeostasis compared to DHA, owing to its stronger upregulation of Sirt3. These results indicate that DHA and EPA can efficaciously alleviate seizure-induced cognitive deficiency by inhibiting ferroptosis in PTZ-kindled young mice.
Topics: Humans; Child; Animals; Mice; Infant, Newborn; Pentylenetetrazole; Docosahexaenoic Acids; Eicosapentaenoic Acid; Sirtuin 3; Seizures; Cognition; Disease Models, Animal
PubMed: 37755077
DOI: 10.3390/md21090464 -
Prostaglandins, Leukotrienes, and... Jan 2015A brief overview of the evidence for omega-3 fatty acids and, in particular, of docosahexaenoic acid (DHA), involvement in cognition and in dementia is given. Two... (Review)
Review
A brief overview of the evidence for omega-3 fatty acids and, in particular, of docosahexaenoic acid (DHA), involvement in cognition and in dementia is given. Two studies are presented in this regard in which the key intervention is a DHA supplement. The fist, the MIDAS Study demonstrated that DHA can be of benefit for episodic memory in healthy adults with a mild memory complaint. The second, the ADCS AD trial found no benefit of DHA in the primary outcomes but found an intriguing benefit for cognitive score in ApoE4 negative allele patients. This leads to a consideration of the mechanisms of action and role of ApoE and its modulation by DHA. Given the fundamental role of ApoE in cellular lipid transport and metabolism in the brain and periphery, it is no surprise that ApoE affects n-3 PUFA brain function as well. It remains to be seen to what extent ApoE4 deleterious effect in AD is associated with n-3 PUFA-related cellular mechanisms in the brain and, more specifically, whether ApoE4 directly impairs the transport of DHA into the brain, as has been suggested.
Topics: Aging; Animals; Brain; Cognition; Dementia; Docosahexaenoic Acids; Humans; Neuroprotective Agents; Randomized Controlled Trials as Topic
PubMed: 25457546
DOI: 10.1016/j.plefa.2014.10.003 -
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 -
Scientific Reports Nov 2023Age-related macular degeneration (AMD) is a complex disease caused by different genetic and environmental risk factors leading to loss of cells in the central part of...
Age-related macular degeneration (AMD) is a complex disease caused by different genetic and environmental risk factors leading to loss of cells in the central part of the retina. Oxidative stress appears to be an important environmental risk factor that contributes to both the initiation and progression of AMD. Retinal pigment epithelium (RPE) plays an important role in regulating oxidative stress in the retina and is one of the main retinal cell types affected in AMD. A main function of RPE is to phagocytose photoreceptor outer segments (POS) which are rich in the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA), making this cell type potentially more susceptible to oxidative stress-induced lipid peroxidation which can lead to cell death. RPE is known to undergo necrotic cell death in response to oxidative stress. The aim of this study was to determine if DHA in POS can increase oxidative damage to RPE. It was found that RPE undergo increased lipid peroxidation and decreased cell viability when stressed with hydrogen peroxide in combination with DHA or POS. HO-induced oxidative stress was found to cause both ferroptosis and necroptosis. However, the ferroptosis regulator acyl-CoA synthetase long-chain family member 4 (ACSL4) was found to be downregulated in RPE exposed to HO and this effect was exacerbated when the RPE cells were simultaneously treated with DHA. Together, these results show a response of RPE when stressed which will likely be overwhelmed under disease conditions such as AMD resulting in cell death.
Topics: Humans; Retinal Pigment Epithelium; Docosahexaenoic Acids; Ferroptosis; Hydrogen Peroxide; Necroptosis; Oxidative Stress; Macular Degeneration
PubMed: 38036571
DOI: 10.1038/s41598-023-47721-5 -
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 -
Nutrients Nov 2023Fatty fish, which include mackerel, herring, salmon and sardines, and certain species of algae (e.g., sp., and ) are the only naturally rich sources of the omega-3... (Review)
Review
Fatty fish, which include mackerel, herring, salmon and sardines, and certain species of algae (e.g., sp., and ) are the only naturally rich sources of the omega-3 polyunsaturated fatty acids (-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are the most biologically active members of the -3 PUFA family. Limited dietary sources and fluctuating content of EPA and DHA in fish raise concerns about the status of EPA and DHA among athletes, as confirmed in a number of studies. The beneficial effects of EPA and DHA include controlling inflammation, supporting nervous system function, maintaining muscle mass after injury and improving training adaptation. Due to their inadequate intake and beneficial health-promoting effects, athletes might wish to consider using supplements that provide EPA and DHA. Here, we provide an overview of the effects of EPA and DHA that are relevant to athletes and discuss the pros and cons of supplements as a source of EPA and DHA for athletes.
Topics: Humans; Animals; Eicosapentaenoic Acid; Docosahexaenoic Acids; Fatty Acids, Omega-3; Dietary Supplements; Fishes; Athletes
PubMed: 38068783
DOI: 10.3390/nu15234925 -
Amelioration of Cognitive and Olfactory System Deficits in APOE4 Transgenic Mice with DHA Treatment.Molecular Neurobiology Oct 2023Olfactory dysfunction and atrophy of olfactory brain regions are observed early in mild cognitive impairment and Alzheimer disease. Despite substantial evidence showing...
Olfactory dysfunction and atrophy of olfactory brain regions are observed early in mild cognitive impairment and Alzheimer disease. Despite substantial evidence showing neuroprotective effects in MCI/AD with treatment of docosahexaenoic acid (DHA), an omega-3 fatty acid, few studies have assessed DHA and its effects on the olfactory system deficits. We therefore performed structural (MRI), functional (olfactory behavior, novel object recognition), and molecular (markers of apoptosis and inflammation) assessments of APOE4 and wild-type mice ± DHA treatment at 3, 6, and 12 months of age. Our results demonstrate that APOE4 mice treated with the control diet show recognition memory deficits, abnormal olfactory habituation, and discrimination abilities and an increase in IBA-1 immunoreactivity in the olfactory bulb. These phenotypes were not present in APOE4 mice treated with a DHA diet. Alterations in some brain regions' weights and/or volumes were observed in the APOPE4 mice and may be due to caspase activation and/or neuroinflammatory events. These results suggest that the consumption of a diet rich in DHA may provide some benefit to E4 carriers but may not alleviate all symptoms.
Topics: Mice; Animals; Mice, Transgenic; Docosahexaenoic Acids; Apolipoprotein E4; Brain; Cognitive Dysfunction; Alzheimer Disease; Cognition
PubMed: 37329383
DOI: 10.1007/s12035-023-03401-z -
European Review For Medical and... Jul 2020Although inflammation is protective of the body, uncontrolled acute inflammatory reactions may inflict tissue damage and lead to chronic inflammation. There is a... (Review)
Review
Although inflammation is protective of the body, uncontrolled acute inflammatory reactions may inflict tissue damage and lead to chronic inflammation. There is a fast-growing research interest in mechanisms that mediate regression of inflammation and actions of anti-inflammatory factors. Studies of inflammatory and anti-inflammatory mechanisms have uncovered roles for new lipid mediators, including lipoxins, resolvins, protectins, and maresins, collectively referred to as specialized pro-resolving mediators (SPM). Maresins have recently been discovered and are biosynthesized from docosahexaenoic acid (DHA) by macrophages and display strong anti-inflammatory and pro-resolving activities. Here, we summarize the actions and mechanisms of maresins in different diseases and suggest possible therapeutic uses.
Topics: Animals; Anti-Inflammatory Agents; Docosahexaenoic Acids; Humans; Inflammation; Inflammation Mediators; Signal Transduction
PubMed: 32706084
DOI: 10.26355/eurrev_202007_21913