-
Current Opinion in Clinical Nutrition... Mar 2021Docosapentaenoic acid (DPA) is a minor omega-3 fatty acid (FA) which has been frequently overlooked in lipid research. This review examines the biochemical and... (Review)
Review
PURPOSE OF REVIEW
Docosapentaenoic acid (DPA) is a minor omega-3 fatty acid (FA) which has been frequently overlooked in lipid research. This review examines the biochemical and physiological outcomes of human trials which have used pure preparations of DPA (n - 3 DPA) and also recent developments in specialized proresolving lipid mediators (SPMs) derived from n - 3 DPA.
RECENT FINDINGS
There have been only been two human studies and eleven animal studies with pure n - 3 DPA. The doses of n - 3 DPA used in the human trials have been 1-2 g/day. n - 3 DPA abundance is increased in blood lipid fractions within 3-4 days of supplementation. n - 3 DPA has the potential for unique properties, with a greater similarity in biological functioning with docosahexaenoic acid (DHA), than eicosapentaenoic acid (EPA). Despite the typically low levels of n - 3 DPA in most tissue lipids relative to EPA and DHA, unique SPMs, such as resolvins, maresins and protectins of the n - 3 DPA type, are involved in resolution of inflammation and regulating immune function.
SUMMARY
We suggest that measurement of blood levels of n - 3 DPA gives no indication of its broad biological roles, but that the true functionality of this enigmatic n - 3 polyunsaturated fatty acid (PUFA) remains obscure until more is known about the properties of the unique DPA-derived SPMs.
Topics: Animals; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans
PubMed: 33315722
DOI: 10.1097/MCO.0000000000000722 -
Nutrients Dec 2020Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 polyunsaturated fatty acids (PUFAs) consumed in low abundance in the Western diet. Increased... (Review)
Review
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 polyunsaturated fatty acids (PUFAs) consumed in low abundance in the Western diet. Increased consumption of n-3 PUFAs may have beneficial effects for a wide range of physiological outcomes including chronic inflammation. However, considerable mechanistic gaps in knowledge exist about EPA versus DHA, which are often studied as a mixture. We suggest the novel hypothesis that EPA and DHA may compete against each other through overlapping mechanisms. First, EPA and DHA may compete for residency in membrane phospholipids and thereby differentially displace n-6 PUFAs, which are highly prevalent in the Western diet. This would influence biosynthesis of downstream metabolites of inflammation initiation and resolution. Second, EPA and DHA exert different effects on plasma membrane biophysical structure, creating an additional layer of competition between the fatty acids in controlling signaling. Third, DHA regulates membrane EPA levels by lowering its rate of conversion to EPA's elongation product n-3 docosapentaenoic acid. Collectively, we propose the critical need to investigate molecular competition between EPA and DHA in health and disease, which would ultimately impact dietary recommendations and precision nutrition trials.
Topics: Animals; Arachidonic Acid; Diet; Diet, Western; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Humans; Inflammation; Phospholipids
PubMed: 33276463
DOI: 10.3390/nu12123718 -
The Journal of Allergy and Clinical... Nov 2023Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D, and low levels of prostaglandin E. Further,...
BACKGROUND
Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D, and low levels of prostaglandin E. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown.
OBJECTIVE
We sought to determine whether novel lipid mediators are predictive of nasal ILC2 accumulation and symptom scores during COX-1 inhibitor challenge in patients with AERD.
METHODS
Blood and nasal scraping samples from patients with AERD were collected at baseline and COX-1 inhibitor reaction and then processed for flow cytometry for nasal ILC2s and serum for lipidomic analysis.
RESULTS
Eight patients with AERD who were undergoing aspirin desensitization were recruited. Of the 161 eicosanoids tested, 42 serum mediators were detected. Baseline levels of 15-HETE were negatively correlated with the change in numbers of airway ILC2s (r = -0.6667; P = .0428). Docosahexaenoic acid epoxygenase metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) was positively correlated with both changes in airway ILC2s (r = 0.7143; P = .0305) and clinical symptom scores (r = 0.5000; P = .0081).
CONCLUSION
Low levels of baseline 15-HETE predicted a greater accumulation of airway ILC2s in patients with AERD who were receiving COX-1 inhibition. Further, increases in the cytochrome P pathway metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) were associated with increased symptoms and nasal ILC2 accumulation. Future studies to assess how these mediators might control ILC2s may improve the understanding of AERD pathogenesis.
Topics: Humans; Immunity, Innate; Lymphocytes; Asthma, Aspirin-Induced; Hydroxyeicosatetraenoic Acids; Cyclooxygenase Inhibitors; Sinusitis; Nasal Mucosa; Prostaglandins; Eicosanoids; Aspirin; Nasal Polyps
PubMed: 37543185
DOI: 10.1016/j.jaci.2023.06.028 -
Progress in Lipid Research Jul 2023This review is about the role of arachidonic acid (ArA) in foetal and early growth and development. In 1975 and '76, we reported the preferential incorporation of ArA... (Review)
Review
This review is about the role of arachidonic acid (ArA) in foetal and early growth and development. In 1975 and '76, we reported the preferential incorporation of ArA into the developing brain of rat pups, its conservation as a principal component in the brains of 32 mammalian species and the high proportion delivered by the human placenta for foetal nutrition, compared to its parent linoleic acid (LA). ArA is quantitatively the principal acyl component of membrane lipids from foetal red cells, mononuclear cells, astrocytes, endothelium, and placenta. Functionally, we present evidence that ArA, but not DHA, relaxes the foetal mesenteric arteries. The placenta biomagnifies ArA, doubling the proportion of the maternal level in cord blood. The proportions of ArA and its allies (di-homo-gamma-linolenic acid (DGLA), adrenic acid and ω6 docosapentaenoic acid) are similar or higher than the total of ω3 fatty acids in human milk, maintaining the abundant supply to the developing infant. Despite the evidence of the importance of ArA, the European Food Standard Agency, in 2014 rejected the joint FAO and WHO recommendation on the inclusion of ArA in infant formula, although they recommended DHA. The almost universal dominance of ArA in the membrane phosphoglycerides during human organogenesis and prenatal growth suggests that the importance of ArA and its allies in reproductive biology needs to be re-evaluated urgently.
Topics: Pregnancy; Female; Humans; Animals; Rats; Arachidonic Acid; Docosahexaenoic Acids; Linoleic Acid; Infant Formula; Glycerophospholipids; Mammals
PubMed: 36746351
DOI: 10.1016/j.plipres.2023.101222 -
Nutrients Dec 2022Docosahexaenoic acid (DHA) is a major constituent of neural and visual membranes and is required for optimal neural and visual function. DHA is derived from food or by... (Review)
Review
Docosahexaenoic acid (DHA) is a major constituent of neural and visual membranes and is required for optimal neural and visual function. DHA is derived from food or by endogenous synthesis from α-linolenic acid (ALA), an essential fatty acid. Low blood levels of DHA in some westernised populations have led to speculations that child development disorders and various neurological conditions are associated with sub-optimal neural DHA levels, a proposition which has been supported by the supplement industry. This review searched for evidence of deficiency of DHA in human populations, based on elevated levels of the biochemical marker of -3 deficiency, docosapentaenoic acid (22:5-6). Three scenarios/situations were identified for the insufficient supply of DHA, namely in the brain of new-born infants fed with high-linoleic acid (LA), low-ALA formulas, in cord blood of women at birth who were vegetarians and in the milk of women from North Sudan. Twenty post-mortem brain studies from the developed world from adults with various neurological disorders revealed no evidence of raised levels of 22:5-6, even in the samples with reduced DHA levels compared with control subjects. Human populations most likely at risk of -3 deficiency are new-born and weanling infants, children and adolescents in areas of dryland agriculture, in famines, or are refugees, however, these populations have rarely been studied. This is an important topic for future research.
Topics: Infant, Newborn; Infant; Pregnancy; Adult; Child; Humans; Female; Adolescent; Animals; Docosahexaenoic Acids; Fatty Acids, Essential; Brain; Milk; Parturition; alpha-Linolenic Acid
PubMed: 36615819
DOI: 10.3390/nu15010161 -
Journal of Bioscience and Bioengineering Mar 2022ω3-Docosapentaenoic acid (ω3-DPA), an ω3-polyunsaturated fatty acid (ω3-PUFA), is expected to have beneficial physiological functions to humans; however, because of...
ω3-Docosapentaenoic acid (ω3-DPA), an ω3-polyunsaturated fatty acid (ω3-PUFA), is expected to have beneficial physiological functions to humans; however, because of its rarity in nature, it has not been fully analyzed. We isolated an ω3-DPA producing microorganism strain T7 from brackish areas in Japan. Although most oleaginous microorganisms rarely accumulate ω3-DPA (<5% of total lipid), strain T7 accumulated ω3-DPA with more than 20% of total fatty acids. The strain T7 was identified as a related species of Aurantiochytrium. In Aurantiochytrium sp. T7, ω3-DPA production reached 164 mg/L culture broth, and the ω3-DPA content reached 23.5% of the total fatty acids when cultivated in a medium containing 2% glucose as the carbon source and 1% yeast extract as the nitrogen source, with a salinity equivalent to 50% of that of seawater and a pH in the acidic range (pH < 5.5). Aurantiochytrium sp. T7 is a promising producer of high-purity ω3-DPA containing-lipid for the functional analysis of ω3-DPA whose physiological function has hardly been elucidated, and a useful strain for investigating the novel metabolic pathway of fatty acids.
Topics: Culture Media; Docosahexaenoic Acids; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Stramenopiles
PubMed: 34893429
DOI: 10.1016/j.jbiosc.2021.10.011 -
Frontiers in Endocrinology 2023The purpose of this study was to investigate the association between serum polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).
OBJECTIVE
The purpose of this study was to investigate the association between serum polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).
METHODS
We performed a cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. The weighted multiple linear regression model was utilized to determine the association between serum PUFAs and BMD. Further smoothed curve fitting and threshold effect analysis were conducted. Finally, we performed a subgroup analysis.
RESULTS
In total, 1979 participants aged 20-59 years were enrolled. After adjusting for all covariates, we found that serum docosapentaenoic acid (DPA) was positively associated with head BMD (β = 0.0015, 95% Cl: 0.0004, 0.0026, P = 0.008296) and lumbar spine BMD (β = 0.0005, 95% Cl: 0.0000, 0.0010, P = 0.036093), and serum eicosadienoic acid (EDA) was negatively associated with thoracic spine BMD (β = -0.0008, 95% Cl: -0.0016, -0.0000, P = 0.045355). Smoothed curve fitting revealed a nonlinear positive association between serum DPA and lumbar spine BMD. Threshold effect analysis indicated that the threshold of serum DPA was 81.4 µmol/L. Subgroup analysis revealed a positive correlation between serum DPA and head BMD in the subgroup aged 50-59 years (β = 0.0025, 95% Cl: 0.0002, 0.0049, P = 0.035249) and females (β = 0.0026, 95% Cl: 0.0008, 0.0044, P = 0.005005). There was a positive relationship between serum DPA and lumbar spine BMD in females (β = 0.0008, 95% Cl: 0.0001, 0.0015, P = 0.017900) and a negative association between serum EDA and thoracic spine BMD in the subgroup aged 30-39 years (β = -0.0016, 95% Cl: -0.0031, -0.0001, P = 0.041331), males (β = -0.0012, 95% Cl: -0.0023, -0.0001, P = 0.039364) and other races (β = -0.0021, 95% Cl: -0.0037, -0.0006, P = 0.008059).
CONCLUSION
This study demonstrated a linear positive relationship between serum DPA and head BMD, a nonlinear positive association between serum DPA and lumbar spine BMD, and a linear negative correlation between serum EDA and thoracic spine BMD in US adults.
Topics: Male; Female; Humans; Adult; Bone Density; Nutrition Surveys; Absorptiometry, Photon; Cross-Sectional Studies; Fatty Acids, Unsaturated; Lumbar Vertebrae
PubMed: 38047106
DOI: 10.3389/fendo.2023.1266329 -
Nutrients Aug 2022Circulating fatty acids may affect thrombosis but epidemiological data on the associations between fatty acids and risk of venous thromboembolism (VTE) are limited and...
Circulating fatty acids may affect thrombosis but epidemiological data on the associations between fatty acids and risk of venous thromboembolism (VTE) are limited and conflicting. We conducted a Mendelian randomization study to examine the causal associations of 10 circulating fatty acids with VTE risk. Genetic variants strongly associated with ten fatty acids and without linkage disequilibrium were selected as instrumental variables from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Genetic associations for VTE and its subtypes were obtained from the International Network Against Venous Thrombosis Consortium (30,234 cases and 172,122 controls) and the FinnGen study (11,288 VTE cases and 254,771 controls). Estimates from the two data sources were combined. Per standard deviation increase in genetically predicted fatty acid levels, the combined odds ratio (OR) of VTE was 0.88 (95% confidence interval [CI] 0.84-0.92) for α-linolenic acid, 0.92 (95% CI 0.90-0.95) for linoleic acid, 0.85 (95% CI 0.78-0.92) for palmitoleic acid, 0.77 (95% CI 0.77-0.84) for oleic acid, 1.16 (95% CI 1.10-1.23) for eicosapentaenoic acid, 1.10 (95% CI 1.06-1.14) for docosapentaenoic acid, 1.06 (95% CI 1.04-1.08) for arachidonic acid, and 1.19 (95% CI 1.11-1.28) for stearic acid. Genetically predicted levels of docosahexaenoic acid or palmitoleic acid were not associated with VTE risk. Four and eight out of ten genetically predicted fatty acid levels were associated with risk of pulmonary embolism and deep vein thrombosis, respectively. This study suggests that strategies targeting at fatty acids may act as prevention approaches for VTE.
Topics: Fatty Acids; Humans; Mendelian Randomization Analysis; Phospholipids; Risk Factors; Venous Thromboembolism
PubMed: 36014859
DOI: 10.3390/nu14163354 -
Nutrients Oct 2022-3 polyunsaturated fatty acids (-3PUFA) are regarded as viable alternatives to aid the treatment of ulcerative colitis (UC). Most research focuses on eicosapentaenoic...
-3 polyunsaturated fatty acids (-3PUFA) are regarded as viable alternatives to aid the treatment of ulcerative colitis (UC). Most research focuses on eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA); little information is available about the effect of docosapentaenoic acid (DPA) on the gut microbiota and their metabolism in UC mice. In this study, the changes in gut microbiota and their metabolism in UC mice were studied through the 16S rRNA sequencing method and untargeted metabolomics. Moreover, the differential bacterial genus and differential metabolites in responding to DPA supplementation were screened through permutation test after orthogonal partial least squares discriminant analysis (OPLS-DA). The results indicated that DPA supplementation increased the diversity and altered the composition of the gut microbiota in UC mice; , , , and were selected as the differential bacterial genus. Supplementation of DPA also altered the fecal metabolite profile in the UC mice. Moreover, butyrate, -carbamylglutamate (NCG), and histamine were screened as the differential metabolites. In conclusion, the regulation effect of DPA on the gut microbiota and their metabolism might be involved in the intervention mechanism of DPA in UC. More research needs to be carried out to elucidate the mechanism systematically.
Topics: Animals; Bacteria; Butyrates; Colitis, Ulcerative; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Gastrointestinal Microbiome; Histamine; Mice; RNA, Ribosomal, 16S
PubMed: 36235856
DOI: 10.3390/nu14194204 -
PloS One 2023Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty...
Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in free-ranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alpha-linolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolism.
Topics: Animals; alpha-Linolenic Acid; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Linoleic Acid; Myoxidae; Phospholipids; Ursidae; Hibernation
PubMed: 37294822
DOI: 10.1371/journal.pone.0285782