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Journal of Nutritional Science and... 2015Metabolic syndrome is a cluster of metabolic disorders that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic... (Review)
Review
Metabolic syndrome is a cluster of metabolic disorders that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated, dietary lipids have been recognized as contributory factors in the development and the prevention of cardiovascular risk clustering. We investigated the physiological functions and molecular actions of functional lipids, especially omega3-polyunsaturated fatty acid (PUFA)-containing lipids, in the development of metabolic syndrome using obese model animals. Feeding of omega3-PUFA-containing lipids, such as eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, tetracosahexaenoic acid, and omega3-phosphatidylcholine, alleviated hepatic lipid accumulation through the suppression of lipogenic gene expression in the liver. Additionally, dietary omega3-PUFA-containing lipids increased serum adiponectin levels in obese animal models. Their molecular actions in the prevention and alleviation of metabolic syndrome could be attributed to the regulation of the activity or abundance of several transcriptional factors in the liver and adipose tissue. Dietary functional lipids would be useful to prevent or alleviate metabolic syndrome in obese animals. In particular, the function of omega3-containing lipids as dietary adiponectin inducers deserves attention with respect to alleviation of metabolic syndrome by dietary manipulation.
Topics: Adiponectin; Adipose Tissue; Animals; Diet; Fatty Acids, Omega-3; Functional Food; Humans; Liver; Metabolic Syndrome; Obesity; Transcription Factors
PubMed: 26598838
DOI: 10.3177/jnsv.61.S159 -
Animals : An Open Access Journal From... Feb 2023Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have special physiological functions in both brain and retinal tissues that are related to the modulation of inflammatory...
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have special physiological functions in both brain and retinal tissues that are related to the modulation of inflammatory processes and direct effects on neuronal membrane fluidity, impacting mental and visual health. Among them, the long-chain (LC) n-3 PUFAs, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are of special importance. Scarce data are available about the fatty acid (FA) composition of the ruminant brain in response to dietary intervention. However, we decided to examine the brain and retina FA composition of lambs supplemented with an EPA-rich microalga feed for 21 days, as it is known that despite the extensive biohydrogenation of dietary PUFAs in the rumen, ruminants can selectively accumulate some n-3 LC-PUFAs in their brain and retinal tissues. Twenty-eight male lambs were fed a control diet, or the same diet further supplemented with sp. microalga. Their brains and retina were collected for FA characterization. Overall, the brain FA profile remained unchanged, with little alteration in omega-3 docosapentaenoic acid (DPA) enhancement in both the hippocampus and prefrontal cortex. Retinal tissues were particularly responsive to the dietary intervention, with a 4.5-fold enhancement of EPA in the freeze-dried-fed lambs compared with the control lambs. We conclude that retinal tissues are sensitive to short-term n-3 PUFA supplementation in lambs.
PubMed: 36899687
DOI: 10.3390/ani13050828 -
Pain Jun 2023Specialized proresolving mediators (SPMs) have demonstrated potent analgesic actions in animal models of pathological pain. The actions of SPMs in acute and chronic itch...
Novel proresolving lipid mediator mimetic 3-oxa-PD1n-3 docosapentaenoic acid reduces acute and chronic itch by modulating excitatory and inhibitory synaptic transmission and astroglial secretion of lipocalin-2 in mice.
Specialized proresolving mediators (SPMs) have demonstrated potent analgesic actions in animal models of pathological pain. The actions of SPMs in acute and chronic itch are currently unknown. Recently, n-3 docosapentaenoic acid (DPA) was found to be a substrate for the biosynthesis of several novel families of SPMs and 3-oxa-PD1 n-3 DPA (3-oxa-PD1) is an oxidation-resistant metabolic stable analogue of the n-3 DPA-derived protectin D1 (PD1). In this article, we demonstrate that 3-oxa-PD1 effectively reduces both acute and chronic itch in mouse models. Intrathecal injection of 3-oxa-PD1 (100 ng) reduced acute itch induced by histamine, chloroquine, or morphine. Furthermore, intrathecal 3-oxa-PD1 effectively reduced chronic itch, induced by cutaneous T-cell lymphoma (CTCL), allergic contact dermatitis with dinitrofluorobenzene, and psoriasis by imiquimod. Intratumoral injection of 3-oxa-PD1 also suppressed CTCL-induced chronic itch. Strikingly, the antipruritic effect lasted for several weeks after 1-week intrathecal 3-oxa-PD1 treatment. Whole-cell recordings revealed significant increase in excitatory postsynaptic currents in spinal dorsal horn (SDH) neurons of CTCL mice, but this increase was blocked by 3-oxa-PD1. 3-oxa-PD1 further increased inhibitory postsynaptic currents in SDH neurons of CTCL mice. Cutaneous T-cell lymphoma increased the spinal levels of lipocalin-2 (LCN2), an itch mediator produced by astrocytes. 3-oxa-PD1 suppressed LCN2 production in CTCL mice and LCN2 secretion in astrocytes. Finally, CTCL-induced anxiety was alleviated by intrathecal 3-oxa-PD1. Our findings suggest that 3-oxa-PD1 potently inhibits acute and chronic itch through the regulation of excitatory or inhibitory synaptic transmission and astroglial LCN2 production. Therefore, stable SPM analogs such as 3-oxa-PD1 could be useful to treat pruritus associated with different skin injuries.
Topics: Animals; Mice; Astrocytes; Fatty Acids, Unsaturated; Lipocalin-2; Lymphoma, T-Cell, Cutaneous; Mice, Inbred C57BL; Pruritus; Synaptic Transmission
PubMed: 36378290
DOI: 10.1097/j.pain.0000000000002824 -
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 -
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 -
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 -
Lipids Apr 2019The long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in health, but previous National Health and Nutrition...
The long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in health, but previous National Health and Nutrition Examination Survey (NHANES) analyses have shown that EPA and DHA intake in the United States is far below recommendations (~250-500 mg/day EPA + DHA). Less is known about docosapentaenoic acid (DPA), the metabolic intermediate of EPA and DHA; however, evidence suggests DPA may be an important contributor to long-chain n-3 fatty acid intake and impart unique benefits. We used NHANES 2003-2014 data (n = 45,347) to assess DPA intake and plasma concentrations, as well as the relationship between intake and plasma concentrations of EPA, DPA, and DHA. Mean DPA intake was 22.3 ± 0.8 mg/day from 2013 to 2014, and increased significantly over time (p < 0.001), with the lowest values from 2003 to 2004 (16.2 ± 1.2 mg/day). DPA intake was higher in adults (20-55 years) and seniors (55+ years) compared to younger individuals. In regression analyses, DPA intake was a significant predictor of plasma EPA (β = 138.5; p < 0.001) and DHA (β = 318.9; p < 0.001). Plasma DPA was predicted by EPA and DHA intake (β = 13.15; p = 0.001 and β = 7.4; p = 0.002), but not dietary DPA (p = 0.3). This indicates that DPA intake is not a good marker of plasma DPA status (or vice versa), and further research is needed to understand the factors that affect the interconversion of EPA and DPA. These findings have implications for future long-chain n-3 fatty acids dietary recommendations.
Topics: Adolescent; Adult; Child; Cross-Sectional Studies; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Humans; Lipid Metabolism; Male; United States; Young Adult
PubMed: 31025717
DOI: 10.1002/lipd.12146 -
Life (Basel, Switzerland) Apr 2022The associations of fetal fatty acids status to immune-related health parameters later in life are unclear. Our aim is to collect all available information on the... (Review)
Review
The associations of fetal fatty acids status to immune-related health parameters later in life are unclear. Our aim is to collect all available information on the relationship between fatty acid status at birth and allergy in childhood. Systematic literature search was performed on Ovid MEDLINE, Cochrane Library, and Embase. The search retrieved 897 articles without duplicates; 14 articles remained after excluding those that did not fit into our inclusion criteria. When the dichotomous parameter of suffering or not from allergic condition in childhood was analyzed, cord blood eicosapentaenoic acid (EPA) values proved to be significantly lower in allergic than non-allergic children in four comparisons from three studies. When the linear parameters of odds ratios and relative risks for allergy were taken into consideration, high cord blood EPA, but also high docosahexaenoic acid (DHA) and high total n-3 long-chain polyunsaturated fatty acid values were associated to clinically relevant reduction (at least 38%) in eight comparisons from five studies. Within the cord blood samples, higher EPA, docosapentaenoic acid, and DHA values were significantly and negatively associated in eight correlation analyses from three studies with laboratory parameters considered to reflect allergic trait. The data reported here may provide information for defining optimal fatty acid intakes for pregnant women.
PubMed: 35455017
DOI: 10.3390/life12040526 -
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