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Marine Drugs Oct 2022Alzheimer's disease (AD) is a complex and progressive disease, which affects millions of people around the world. Despite the many efforts over the years to find... (Review)
Review
Alzheimer's disease (AD) is a complex and progressive disease, which affects millions of people around the world. Despite the many efforts over the years to find efficient therapeutics, there is no cure yet. Nonetheless, many compounds have been proven to decrease Alzheimer's symptoms. After a short overview of the hypotheses considered in AD drug development and the drugs approved for AD treatment, which lead to symptom release, we focus on the valorization of natural marine sources that decrease AD symptoms, particularly on docosahexaenoic acid (DHA), an important component in membrane phospholipids and the most abundant n-3 polyunsaturated fatty acids (PUFA) found in gray matter of the brain and in retina and on the DHA-containing phospholipids (DHA-PLs) present in marine sources, namely fish, krill, mollusks and in fisheries and aquaculture by-products. DHA-PLs' bioactivities are presented, namely their properties in anti-neurodegeneration, neuroinflammation, as anticancer agents, as well as their benefits to obesity and visual problems. Fisheries and aquaculture by-products are also highlighted as they have a high content of DHA and DHA-rich phospholipids, can be extracted by green methodologies and should be considered in a circular economy for a healthy sustainable future.
Topics: Animals; Docosahexaenoic Acids; Phospholipids; Eicosapentaenoic Acid; Fish Oils; Euphausiacea; Alzheimer Disease
PubMed: 36354985
DOI: 10.3390/md20110662 -
Current Cardiology Reports Nov 2023There has been much debate surrounding the use of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for cardiovascular (CV) risk reduction. (Review)
Review
PURPOSE OF REVIEW
There has been much debate surrounding the use of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for cardiovascular (CV) risk reduction.
RECENT FINDINGS
Recent trials of EPA and DHA have offered conflicting evidence. Some demonstrate reduction in CV risk using EPA alone in select populations. Others have demonstrated no benefit, with potential for side effects, such as new-onset atrial fibrillation. Both EPA and DHA have favorable impact on lipids and inflammation, suggesting some biological plausibility for CV risk reduction. However, clinical trials of these agents have produced mixed results. Based on available evidence, EPA may work better for CV risk than DHA and EPA combined. The benefit of EPA seems to be dose dependent, though higher doses may have more side effects. Further research is needed to define the role of EPA and DHA in the landscape of CV risk reduction.
Topics: Humans; Eicosapentaenoic Acid; Docosahexaenoic Acids; Cardiovascular Diseases; Risk Factors; Heart Disease Risk Factors; Risk Reduction Behavior
PubMed: 37812346
DOI: 10.1007/s11886-023-01972-w -
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 -
International Journal of Molecular... Sep 2023Polyunsaturated fatty acids (PUFAs) undergo lipid peroxidation and conversion into malondialdehyde (MDA). MDA reacts with acetaldehyde to form malondialdehyde-modified...
Lipid Peroxidation of the Docosahexaenoic Acid/Arachidonic Acid Ratio Relating to the Social Behaviors of Individuals with Autism Spectrum Disorder: The Relationship with Ferroptosis.
Polyunsaturated fatty acids (PUFAs) undergo lipid peroxidation and conversion into malondialdehyde (MDA). MDA reacts with acetaldehyde to form malondialdehyde-modified low-density lipoprotein (MDA-LDL). We studied unsettled issues in the association between MDA-LDL and the pathophysiology of ASD in 18 individuals with autism spectrum disorders (ASD) and eight age-matched controls. Social behaviors were assessed using the social responsiveness scale (SRS). To overcome the problem of using small samples, adaptive Lasso was used to enhance the interpretability accuracy, and a coefficient of variation was used for variable selections. Plasma levels of the MDA-LDL levels (91.00 ± 16.70 vs. 74.50 ± 18.88) and the DHA/arachidonic acid (ARA) ratio (0.57 ± 0.16 vs. 0.37 ± 0.07) were significantly higher and the superoxide dismutase levels were significantly lower in the ASD group than those in the control group. Total SRS scores in the ASD group were significantly higher than those in the control group. The unbeneficial DHA/ARA ratio induced ferroptosis via lipid peroxidation. Multiple linear regression analysis and adaptive Lasso revealed an association of the DHA/ARA ratio with total SRS scores and increased MDA-LDL levels in plasma, resulting in neuronal deficiencies. This unbeneficial DHA/ARA-ratio-induced ferroptosis contributes to autistic social behaviors and is available for therapy.
Topics: Humans; Docosahexaenoic Acids; Arachidonic Acid; Autism Spectrum Disorder; Lipid Peroxidation; Ferroptosis; Lipoproteins, LDL; Malondialdehyde
PubMed: 37834244
DOI: 10.3390/ijms241914796 -
Nanomedicine (London, England) Aug 2021
Topics: Docosahexaenoic Acids; Nanomedicine; Nanoparticles; Nanotechnology
PubMed: 34165319
DOI: 10.2217/nnm-2021-0128 -
Kidney360 Dec 2023Increased albuminuria on 5/6 nephrectomized rats, as reported earlier, is attenuated by arachidonic acid–containing and docosahexaenoic acid (DHA)–containing diets....
KEY POINTS
Increased albuminuria on 5/6 nephrectomized rats, as reported earlier, is attenuated by arachidonic acid–containing and docosahexaenoic acid (DHA)–containing diets. This study established that DHA affects both oxidative stress and fibrosis in the kidney. DHA suppressed the oxidative stress and fibrosis, hence suppressing the progression of renal failure.
BACKGROUND
Urinary albumin excretion gradually increases after nephrectomy, which eventually progresses toward renal failure. Our previous study had reported that arachidonic acid (ARA)–containing or docosahexaenoic acid (DHA)–containing diet attenuates the increasing urinary albumin excretion. This study aimed to investigate the effects of ARA-containing or/and DHA-containing diets on oxidative stress and fibrosis that cause kidney injury in 5/6 nephrectomized rats.
METHODS
Sprague–Dawley rats were randomly divided into control group, ARA group, DHA group, and ARA+DHA group. Rats underwent 5/6 kidney removal and were fed ARA-containing or/and DHA-containing diet each five groups continuously for 4 weeks. We collected urine, plasma, and kidney samples 4 weeks after surgery and investigated the effects of ARA-containing and DHA-containing diets on oxidative stress, inflammation, and fibrosis in the kidney.
RESULTS
Urinary albumin excretion, indoxyl sulfate, reactive oxygen species, TNF- levels, and fibrosis in the kidney were all increased on nephrectomy; however, they were attenuated after feeding the rats with DHA-containing diet.
CONCLUSION
One possible mechanism of preventing chronic renal failure would be the suppression of indoxyl sulfate accumulation, oxidative stress, and kidney fibrosis arising due to nephrectomy. The results collectively suggested that DHA-containing diets can suppress the progression of renal failure.
Topics: Rats; Animals; Docosahexaenoic Acids; Diet; Oxidative Stress; Fibrosis
PubMed: 37222582
DOI: 10.34067/KID.0000000000000152 -
Journal of Cardiovascular Pharmacology... Nov 2021Atherosclerotic cardiovascular disease is a significant cause of morbidity and mortality worldwide. While use of statin therapy has improved management of lipids, an... (Review)
Review
BACKGROUND
Atherosclerotic cardiovascular disease is a significant cause of morbidity and mortality worldwide. While use of statin therapy has improved management of lipids, an unmet need in reducing residual atherosclerotic cardiovascular disease risk and ischemic events persists. We provide an overview of the pharmacology of omega-3 fatty acids, omega-3 fatty acid cardiovascular outcomes trials, landmark clinical data and pharmacology of icosapent ethyl (a stable and highly purified ethyl ester of eicosapentaenoic acid), and the critical differences between fish oil supplements and prescription omega-3 fatty acids.
METHOD
A PubMed literature review was conducted in April 2020 to identify articles discussing omega-3 fatty acid cardiovascular outcomes trials, pharmacology of icosapent ethyl, and the evaluation of fish oil dietary supplements and prescription omega-3 fatty acids.
RESULTS
Both eicosapentaenoic acid and docosahexaenoic acid have been widely associated with positive health benefits; however, data are inconsistent regarding the benefit of combination eicosapentaenoic acid and docosahexaenoic acid in patients with cardiovascular disease. Eicosapentaenoic acid, and specifically icosapent ethyl, has demonstrated atherosclerotic cardiovascular disease risk reduction among statin-treated patients. Important clinical differences exist between dietary supplement and prescription omega-3 fatty acid products.
CONCLUSIONS
As research regarding the optimal management of dyslipidemia continues, additional therapy beyond statins is necessary to reduce atherosclerotic cardiovascular disease risk. In large cardiovascular outcomes trials, eicosapentaenoic acid has demonstrated cardiovascular benefit. Icosapent ethyl possesses a favorable efficacy and safety profile and should be considered as an adjunct to statin therapy to reduce ischemic event risk.
Topics: Atherosclerosis; Cardiovascular Diseases; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; Pharmacists
PubMed: 34191622
DOI: 10.1177/10742484211023715 -
Journal of Agricultural and Food... Jun 2023Goat milk is increasingly recognized by consumers due to its high nutritional value, richness in short- and medium-chain fatty acids, and richness in polyunsaturated...
Goat milk is increasingly recognized by consumers due to its high nutritional value, richness in short- and medium-chain fatty acids, and richness in polyunsaturated fatty acids (PUFA). Exogenous supplementation of docosahexaenoic acid (DHA) is an important approach to increasing the content of PUFA in goat milk. Several studies have reported benefits of dietary DHA in terms of human health, including potential against chronic diseases and tumors. However, the mechanisms whereby an increased supply of DHA regulates mammary cell function is unknown. In this study, we investigated the effect of DHA on lipid metabolism processes in goat mammary epithelial cells (GMEC) and the function of H3K9ac epigenetic modifications in this process. Supplementation of DHA promoted lipid droplet accumulation increased the DHA content and altered fatty acid composition in GMEC. Lipid metabolism processes were altered by DHA supplementation through transcriptional programs in GMEC. ChIP-seq analysis revealed that DHA induced genome-wide H3K9ac epigenetic changes in GMEC. Multiomics analyses (H3K9ac genome-wide screening and RNA-seq) revealed that DHA-induced expression of lipid metabolism genes (, , , , , , ), which were closely related with changes in lipid metabolism processes and fatty acid profiles, were regulated by modification of H3K9ac. In particular, DHA increased the enrichment of H3K9ac in the promoter region of and promoted its transcription, while inhibited lipid synthesis and activated AMPK signaling in GMEC. The activation of the expression of fatty acid metabolism-related genes , , and and their upstream transcription factor by the AMPK inhibitor was attenuated in -overexpressing GMEC. In conclusion, DHA alters lipid metabolism processes via H3K9ac modifications and the PDK4-AMPK-SREBP1 signaling axis in goat mammary epithelial cells, providing new insights into the mechanism through which DHA affects mammary cell function and regulates milk fat metabolism.
Topics: Humans; Animals; Lipid Metabolism; Docosahexaenoic Acids; AMP-Activated Protein Kinases; Triglycerides; Fatty Acids; Fatty Acids, Unsaturated; Epigenesis, Genetic; Goats; Mammary Glands, Animal; Epithelial Cells; Phosphatidate Phosphatase
PubMed: 37224334
DOI: 10.1021/acs.jafc.3c01606 -
Nutrients Oct 2022Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-omega-3 fatty acids with various functions-influence sleep in children and young adults. However, only limited... (Randomized Controlled Trial)
Randomized Controlled Trial
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-omega-3 fatty acids with various functions-influence sleep in children and young adults. However, only limited studies on their effects on sleep in middle- and old-aged adults have been reported. Therefore, we investigated the effects of DHA and EPA on sleep quality in subjects aged ≥ 45 years. We performed a randomized, placebo-controlled, double-blinded, parallel-grouped study, in which we randomly assigned 66 healthy Japanese males and females. Each individual received six 480 mg capsules containing 576 mg DHA and 284 mg EPA per day (DHA/EPA group, = 33), or corn oil (placebo group, = 33), for 12 weeks. Before and after the intervention, the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA) and the sleep state test were conducted. In the DHA/EPA group, factor III (frequent dreaming) scores among the OSA-MA scores were significantly improved compared to the placebo group. Additionally, sleep state tests revealed that sleep efficiency improved in the DHA/EPA group. To our knowledge, this study is the first to report that DHA/EPA improves sleep quality in middle- and old-aged individuals, even at doses lower than those administered in previous studies.
Topics: Aged; Capsules; Corn Oil; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Healthy Volunteers; Humans; Male; Middle Aged; Sleep Apnea, Obstructive; Sleep Quality; Thromboplastin
PubMed: 36235788
DOI: 10.3390/nu14194136 -
Marine Drugs Sep 2021Thraustochytrids are unicellular, heterotrophic marine eukaryotes. Some species are known to store surplus carbon as intracellular lipids, and these also contain the... (Review)
Review
Thraustochytrids are unicellular, heterotrophic marine eukaryotes. Some species are known to store surplus carbon as intracellular lipids, and these also contain the long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA). Most vertebrates are unable to synthesize sufficient amounts of DHA, and this fatty acid is essential for, e.g., marine fish, domesticated animals, and humans. Thraustochytrids may also produce other commercially valuable fatty acids and isoprenoids. Due to the great potential of thraustochytrids as producers of DHA and other lipid-related molecules, a need for more knowledge on this group of organisms is needed. This necessitates the ability to do genetic manipulation of the different strains. Thus far, this has been obtained for a few strains, while it has failed for other strains. Here, we systematically review the genetic transformation methods used for different thraustochytrid strains, with the aim of aiding studies on strains not yet successfully transformed. The designs of transformation cassettes are also described and compared. Moreover, the potential problems when trying to establish transformation protocols in new thraustochytrid species/strains are discussed, along with suggestions utilized in other organisms to overcome similar challenges. The approaches discussed in this review could be a starting point when designing protocols for other non-model organisms.
Topics: Animals; Aquatic Organisms; Docosahexaenoic Acids; Genetic Engineering; Microalgae
PubMed: 34564177
DOI: 10.3390/md19090515