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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 -
Progress in Lipid Research Jul 2015Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate... (Review)
Review
Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate exists as to whether DHA synthesized from ALA can provide sufficient DHA for the adult brain, as measures of DHA synthesis from ingested ALA are typically <1% of the oral ALA dose. However, the primary fate of orally administered ALA is β-oxidation and long-term storage in adipose tissue, suggesting that DHA synthesis measures involving oral ALA tracer ingestion may underestimate total DHA synthesis. There is also evidence that DHA synthesized from ALA can meet brain DHA requirements, as animals fed ALA-only diets have brain DHA concentrations similar to DHA-fed animals, and the brain DHA requirement is estimated to be only 2.4-3.8 mg/day in humans. This review summarizes evidence that DHA synthesis from ALA can provide sufficient DHA for the adult brain by examining work in humans and animals involving estimates of DHA synthesis and brain DHA requirements. Also, an update on methods to measure DHA synthesis in humans is presented highlighting a novel approach involving steady-state infusion of stable isotope-labeled ALA that bypasses several limitations of oral tracer ingestion. It is shown that this method produces estimates of DHA synthesis that are at least 3-fold higher than brain uptake rates in rats.
Topics: Animals; Biosynthetic Pathways; Brain; Diet; Docosahexaenoic Acids; Humans; alpha-Linolenic Acid
PubMed: 25920364
DOI: 10.1016/j.plipres.2015.04.002 -
Journal of Oleo Science Oct 2021Dietary fish oil containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been reported to affect the diversity and composition of gut microbiota and...
Dietary fish oil containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been reported to affect the diversity and composition of gut microbiota and bacterial metabolites. However, few reports have focused on the effects of EPA and DHA on gut microbiota diversity and bacterial metabolites. This study evaluated the effects of dietary EPA-ethyl ester (EE) and DHA-EE on steroid metabolism, gut microbiota, and bacterial metabolites in Wistar rats. Male rats were fed the experimental diets containing 5% (w/w) soybean oil-EE (SOY diet), EPA-EE (EPA diet), and DHA-EE (DHA diet) for four weeks. The lipid contents in the serum and liver, mRNA expression levels in the liver, and the diversity, composition, and metabolites of the gut microbiota were evaluated. The EPA and DHA diets decreased serum and liver cholesterol contents compared to the SOY diet. In addition, there were no significant changes in gene expression levels related to steroid metabolism in the liver between the EPA and DHA groups. Rats fed the DHA diet had lower microbiota diversity indices, such as Simpson and Shannon indices, than rats fed the SOY and EPA diets. In addition, rats fed EPA and DHA had significant differences in the relative abundance of microbiota at the genus level, such as Phascolarctobacterium, Turicibacter, and [Eubacterium]. Therefore, it was concluded that EPA and DHA have different effects on the diversity and composition of gut microbiota under the experimental conditions employed herein.
Topics: Animals; Bacteria; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Esters; Eubacterium; Firmicutes; Gastrointestinal Microbiome; Lipid Metabolism; Liver; Male; Microbiota; Rats, Wistar; Veillonellaceae; Rats
PubMed: 34497184
DOI: 10.5650/jos.ess21189 -
Nutrients Aug 2020One of the characteristic features of aging is the progressive loss of muscle mass, a nosological syndrome called sarcopenia. It is also a pathologic risk factor for... (Review)
Review
One of the characteristic features of aging is the progressive loss of muscle mass, a nosological syndrome called sarcopenia. It is also a pathologic risk factor for many clinically adverse outcomes in older adults. Therefore, delaying the loss of muscle mass, through either boosting muscle protein synthesis or slowing down muscle protein degradation using nutritional supplements could be a compelling strategy to address the needs of the world's aging population. Here, we review the recently identified properties of docosahexaenoic acid (DHA). It was shown to delay muscle wasting by stimulating intermediate oxidative stress and inhibiting proteasomal degradation of muscle proteins. Both the ubiquitin-proteasome and the autophagy-lysosome systems are modulated by DHA. Collectively, growing evidence indicates that DHA is a potent pharmacological agent that could improve muscle homeostasis. Better understanding of cellular proteolytic systems associated with sarcopenia will allow us to identify novel therapeutic interventions, such as omega-3 polyunsaturated fatty acids, to treat this disease.
Topics: Aging; Autophagy; Docosahexaenoic Acids; Humans; Lysosomes; Proteasome Endopeptidase Complex; Sarcopenia; Ubiquitin
PubMed: 32859116
DOI: 10.3390/nu12092597 -
Nutrients Jun 2021In this special issue, we have focused on the maternal docosahexaenoic acid, 22:6n-3 (DHA), on children's neurodevelopment [...].
In this special issue, we have focused on the maternal docosahexaenoic acid, 22:6n-3 (DHA), on children's neurodevelopment [...].
Topics: Breast Feeding; Child; Child Development; Dietary Supplements; Docosahexaenoic Acids; Female; Humans; Lactation; Nervous System Diseases
PubMed: 34199063
DOI: 10.3390/nu13072209 -
Journal of Colloid and Interface Science Sep 2024Infectious diseases, particularly those associated with biofilms, are challenging to treat due to an increased tolerance to commonly used antibiotics. This underscores...
Infectious diseases, particularly those associated with biofilms, are challenging to treat due to an increased tolerance to commonly used antibiotics. This underscores the urgent need for innovative antimicrobial strategies. Here, we present an alternative simple-by-design approach focusing on the development of biocompatible and antibiotic-free nanocarriers from docosahexaenoic acid (DHA) that has the potential to combat microbial infections and phosphatidylglycerol (DOPG), which is attractive for use as a biocompatible prominent amphiphilic component of Gram-positive bacterial cell membranes. We assessed the anti-bacterial and anti-biofilm activities of these nanoformulations (hexosomes and vesicles) against S. aureus and S. epidermidis, which are the most common causes of infections on catheters and medical devices by different methods (including resazurin assay, time-kill assay, and confocal laser scanning microscopy on an in vitro catheter biofilm model). In a DHA-concentration-dependent manner, these nano-self-assemblies demonstrated strong anti-bacterial and anti-biofilm activities, particularly against S. aureus. A five-fold reduction of the planktonic and a four-fold reduction of biofilm populations of S. aureus were observed after treatment with hexosomes. The nanoparticles had a bacteriostatic effect against S. epidermidis planktonic cells but no anti-biofilm activity was detected. We discuss the findings in terms of nanoparticle-bacterial cell interactions, plausible alterations in the phospholipid membrane composition, and potential penetration of DHA into these membranes, leading to changes in their structural and biophysical properties. The implications for the future development of biocompatible nanocarriers for the delivery of DHA alone or in combination with other anti-bacterial agents are discussed, as novel treatment strategies of Gram-positive infections, including biofilm-associated infections.
Topics: Biofilms; Anti-Bacterial Agents; Phosphatidylglycerols; Staphylococcus aureus; Nanoparticles; Docosahexaenoic Acids; Staphylococcus epidermidis; Microbial Sensitivity Tests; Liquid Crystals; Particle Size
PubMed: 38729002
DOI: 10.1016/j.jcis.2024.04.186 -
International Journal of Molecular... Oct 2017Acute pancreatitis refers to the sudden inflammation of the pancreas. It is associated with premature activation and release of digestive enzymes into the pancreatic... (Review)
Review
Acute pancreatitis refers to the sudden inflammation of the pancreas. It is associated with premature activation and release of digestive enzymes into the pancreatic interstitium and systemic circulation, resulting in pancreatic tissue autodigestion and multiple organ dysfunction, as well as with increased cytokine production, ultimately leading to deleterious local and systemic effects. Although mechanisms involved in pathogenesis of acute pancreatitis have not been completely elucidated, oxidative stress is regarded as a major risk factor. In human acute pancreatitis, lipid peroxide levels in pancreatic tissues increase. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (C22:6n-3), exerts anti-inflammatory and antioxidant effects on various cells. Previous studies have shown that DHA activates peroxisome proliferator-activated receptor-γ and induces catalase, which inhibits oxidative stress-mediated inflammatory signaling required for cytokine expression in experimental acute pancreatitis using cerulein. Cerulein, a cholecystokinin analog, induces intra-acinar activation of trypsinogen in the pancreas, which results in human acute pancreatitis-like symptoms. Therefore, DHA supplementation may be beneficial for preventing or inhibiting acute pancreatitis development. Since DHA reduces serum triglyceride levels, addition of DHA to lipid-lowering drugs like statins has been investigated to reduce hypertriglyceridemic acute pancreatitis. However, high DHA concentrations increase cytosolic Ca, which activates protein kinase C and may induce hyperlipidemic acute pancreatitis. In this review, effect of DHA on cerulein-induced and hypertriglyceridemic acute pancreatitis has been discussed. The relation of high concentration of DHA to hyperlipidemic acute pancreatitis has been included.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ceruletide; Docosahexaenoic Acids; Humans; Hypertriglyceridemia; Pancreatitis
PubMed: 29068376
DOI: 10.3390/ijms18112239 -
Frontiers in Immunology 2022Docosahexaenoic acid (DHA) is an omega-3 fatty acid that has a range of positive impacts on human health, including anti-inflammatory effects and inhibition of...
Docosahexaenoic acid (DHA) is an omega-3 fatty acid that has a range of positive impacts on human health, including anti-inflammatory effects and inhibition of osteoclast formation G-protein-coupled receptor 120 (GPR120). Orthodontic force was reported to induce tumor necrosis factor-α (TNF-α) expression, which activates osteoclast differentiation during orthodontic tooth movement (OTM). The aim of this study was to investigate the influence of DHA on TNF-α-induced osteoclast formation and OTM . We examined osteoclast formation and bone resorption within the calvaria of both wild-type (WT) and GPR120-deficient (GPR120-KO) mice injected with phosphate-buffered saline (PBS), TNF-α, TNF-α and DHA, or DHA. DHA inhibited TNF-α-induced osteoclast formation and bone resorption in WT mice but had no effect in GPR120-KO mice. OTM experiments were performed in mouse strains with or without regular injection of DHA, and the effects of DHA on osteoclast formation in the alveolar bones during OTM were examined. DHA also suppressed OTM in WT but not GPR120-KO mice. Our data showed that DHA suppresses TNF-α-induced osteoclastogenesis and bone resorption GPR120. TNF-α has considerable significance in OTM, and therefore, DHA may also inhibit TNF-α-induced osteoclast formation and bone resorption in OTM.
Topics: Animals; Mice; Bone Resorption; Docosahexaenoic Acids; Osteoclasts; Receptors, G-Protein-Coupled; Tooth Movement Techniques; Tumor Necrosis Factor-alpha
PubMed: 36741381
DOI: 10.3389/fimmu.2022.929690 -
Dose-effect and metabolism of docosahexaenoic acid: pathophysiological relevance in blood platelets.Prostaglandins, Leukotrienes, and... Jan 2013Docosahexaenoic acid (DHA) is known as a major nutrient from marine origin. Considering its beneficial effect in vascular risk prevention, the effect of DHA on blood... (Review)
Review
Docosahexaenoic acid (DHA) is known as a major nutrient from marine origin. Considering its beneficial effect in vascular risk prevention, the effect of DHA on blood components, especially platelets, will be reviewed here. Investigating the dose-effect of DHA in humans shows that daily intake lower than one gram/day brings several benefits, such as inhibition of platelet aggregation, resistance of monocytes against apoptosis, and reinforced antioxidant status in platelets and low-density lipoproteins. However, higher daily intake may be less efficient on those parameters, especially by losing the antioxidant effect. On the other hand, a focus on the inhibition of platelet aggregation by lipoxygenase end-products of DHA is made. The easy conversion of DHA by lipoxygenases and the formation of a double lipoxygenation product named protectin DX, reveal an original way for DHA to contribute in platelet inhibition through both the cyclooxygenase inhibition and the antagonism of thromboxane A₂ action.
Topics: Animals; Antioxidants; Blood Platelets; Dietary Supplements; Docosahexaenoic Acids; Humans; Lipid Peroxidation; Lipoproteins, LDL; Lipoxygenases; Oxidants; Platelet Aggregation; Platelet Aggregation Inhibitors
PubMed: 22520055
DOI: 10.1016/j.plefa.2012.04.001 -
The Journal of Nutrition Dec 2019Dietary DHA intake among US toddlers is low. Healthy physical growth is an important objective for the clinical care of children born preterm. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Dietary DHA intake among US toddlers is low. Healthy physical growth is an important objective for the clinical care of children born preterm.
OBJECTIVES
The aim of the trial was to examine the effects of supplementing toddlers born preterm with DHA and arachidonic acid (AA) for 180 d on growth and adiposity.
METHODS
Omega Tots, a randomized placebo-controlled trial, was conducted between April 2012 and March 2017. Children born at <35 wk gestation who were 10-16 mo in corrected age were assigned to receive daily oral supplements of DHA and AA (200 mg each, "DHA + AA") or corn oil (placebo) for 180 d. Prespecified secondary outcomes included weight, length, head circumference, mid-upper arm circumference, triceps and subscapular skinfolds, BMI, and their respective z scores, and body fat percentage, which were measured at baseline and trial completion. Mixed-effects regression was used to compare the change in outcomes between the DHA + AA and placebo groups, controlling for baseline values.
RESULTS
Among 377 children included in the analysis (median corrected age = 15.7 mo, 48.3% female), 348 (92.3%) had growth or adiposity data at baseline and trial end. No statistically significant differences between the DHA + AA and placebo groups in growth or adiposity outcomes were observed. For instance, the change in weight-for-age z scores was 0.1 for the DHA + AA group and 0.0 for the placebo group (effect size = 0.01, P = 0.99). However, post-hoc subgroup analyses revealed a statistically significant interaction between treatment group and sex, suggesting somewhat slower linear growth for females assigned to the DHA + AA group compared with the placebo group.
CONCLUSIONS
Among toddlers born preterm, daily supplementation with DHA + AA for 180 d resulted in no short-term differences in growth or adiposity compared with placebo. If DHA supplementation is implemented after the first year of life, it can be expected to have no effect on short-term growth or adiposity. This trial is registered with clinicaltrials.gov as NCT02199808.
Topics: Adiposity; Arachidonic Acids; Docosahexaenoic Acids; Double-Blind Method; Female; Growth; Guideline Adherence; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Placebos
PubMed: 31187863
DOI: 10.1093/jn/nxz115