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Nutrients Jul 2017The associations between -3 polyunsaturated fatty acids (PUFAs) and metabolic syndrome (MetS) risk have demonstrated inconsistent results. The present study aimed to... (Meta-Analysis)
Meta-Analysis Review
The associations between -3 polyunsaturated fatty acids (PUFAs) and metabolic syndrome (MetS) risk have demonstrated inconsistent results. The present study aimed to investigate whether higher circulating -3 PUFAs and dietary -3 PUFAs intake have a protective effect on MetS risk. A systematic literature search in the PubMed, Scopus, and Chinese National Knowledge Infrastructure (CNKI) databases was conducted up to March 2017. Odd ratios (ORs) from case-control and cross-sectional studies were combined using a random-effects model for the highest versus lowest category. The differences of -3 PUFAs between healthy subjects and patients with MetS were calculated as weighted mean difference (WMD) by using a random-effects model. Seven case-control and 20 cross-sectional studies were included. A higher plasma/serum -3 PUFAs was associated with a lower MetS risk (Pooled OR = 0.63, 95% CI: 0.49, 0.81). The plasma/serum -3 PUFAs in controls was significantly higher than cases (WMD: 0.24; 95% CI: 0.04, 0.43), especially docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). However, no significant association was found between dietary intake of -3 PUFAs or fish and MetS risk. The present study provides substantial evidence of a higher circulating -3 PUFAs associated with a lower MetS risk. The circulating -3 PUFAs can be regarded as biomarkers indicating MetS risk, especially DPA and DHA.
Topics: Fatty Acids, Omega-3; Humans; Metabolic Syndrome; Odds Ratio; Risk Factors
PubMed: 28684692
DOI: 10.3390/nu9070703 -
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 Physiology 2021Arachidonic acid (ARA) is an important ω-6 polyunsaturated fatty acid (PUFA), and docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid... (Review)
Review
Arachidonic acid (ARA) is an important ω-6 polyunsaturated fatty acid (PUFA), and docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA) are three well-known ω-3 PUFAs. These fatty acids can be metabolized into a number of bioactive lipids. Eicosanoids derived from ARA have drawn great attention because of their important and complex biofunctions. Although EPA, DHA and n-3 DPA have also shown powerful biofunctions, we have fewer studies of metabolites derived from them than those from ARA. Recently, growing research has focused on the bioaction of ω-3 PUFA-derived metabolites, which indicates their great potential for treating metabolic disorders. Most of the functional studies of these bioactive lipids focused on their anti-inflammatory effects. However, several studies elucidated their direct effects on pancreatic β cells, hepatocytes, adipocytes, skeletal muscle cells, and endothelial cells. These researches revealed the importance of studying the functions of metabolites derived from ω-3 polyunsaturated fatty acids other than themselves. The current review summarizes research into the effects of ω-3 PUFA-derived oxylipins on metabolic disorders, including diabetes, non-alcoholic fatty liver disease, adipose tissue dysfunction, and atherosclerosis.
PubMed: 34113260
DOI: 10.3389/fphys.2021.646491 -
Frontiers in Immunology 2020Neuroinflammation plays a crucial role in the development and progression of Alzheimer's disease (AD), in which activated microglia are found to be associated with...
The Novel Omega-6 Fatty Acid Docosapentaenoic Acid Positively Modulates Brain Innate Immune Response for Resolving Neuroinflammation at Early and Late Stages of Humanized APOE-Based Alzheimer's Disease Models.
Neuroinflammation plays a crucial role in the development and progression of Alzheimer's disease (AD), in which activated microglia are found to be associated with neurodegeneration. However, there is limited evidence showing how neuroinflammation and activated microglia are directly linked to neurodegeneration . Besides, there are currently no effective anti-inflammatory drugs for AD. In this study, we report on an effective anti-inflammatory lipid, linoleic acid (LA) metabolite docosapentaenoic acid (DPAn-6) treatment of aged humanized EFAD mice with advanced AD pathology. We also report the associations of neuroinflammatory and/or activated microglial markers with neurodegeneration . First, we found that dietary LA reduced proinflammatory cytokines of IL1-β, IL-6, as well as mRNA expression of COX2 toward resolving neuroinflammation with an increase of IL-10 in adult AD models E3FAD and E4FAD mice. Brain fatty acid assays showed a five to six-fold increase in DPAn-6 by dietary LA, especially more in E4FAD mice, when compared to standard diet. Thus, we tested DPAn-6 in aged E4FAD mice. After DPAn-6 was administered to the E4FAD mice by oral gavage for three weeks, we found that DPAn-6 reduced microgliosis and mRNA expressions of inflammatory, microglial, and caspase markers. Further, DPAn-6 increased mRNA expressions of ADCYAP1, VGF, and neuronal pentraxin 2 in parallel, all of which were inversely correlated with inflammatory and microglial markers. Finally, both LA and DPAn-6 directly reduced mRNA expression of COX2 in amyloid-beta42 oligomer-challenged BV2 microglial cells. Together, these data indicated that DPAn-6 modulated neuroinflammatory responses toward resolution and improvement of neurodegeneration in the late stages of AD models.
Topics: Alzheimer Disease; Animals; Apolipoproteins E; Brain; Cytokines; Disease Models, Animal; Disease Susceptibility; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Immunity, Innate; Immunohistochemistry; Inflammation Mediators; Mice; Mice, Transgenic; Microglia; Neurodegenerative Diseases
PubMed: 33178186
DOI: 10.3389/fimmu.2020.558036 -
Foods (Basel, Switzerland) Jan 2021Epithelial cells (enterocytes) form part of the intestinal barrier, the largest human interface between the internal and external environments, and responsible for... (Review)
Review
Epithelial cells (enterocytes) form part of the intestinal barrier, the largest human interface between the internal and external environments, and responsible for maintaining regulated intestinal absorption and immunological control. Under inflammatory conditions, the intestinal barrier and its component enterocytes become inflamed, leading to changes in barrier histology, permeability, and chemical mediator production. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) can influence the inflammatory state of a range of cell types, including endothelial cells, monocytes, and macrophages. This review aims to assess the current literature detailing the effects of ω-3 PUFAs on epithelial cells. Marine-derived ω-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid, as well as plant-derived alpha-linolenic acid, are incorporated into intestinal epithelial cell membranes, prevent changes to epithelial permeability, inhibit the production of pro-inflammatory cytokines and eicosanoids and induce the production of anti-inflammatory eicosanoids and docosanoids. Altered inflammatory markers have been attributed to changes in activity and/or expression of proteins involved in inflammatory signalling including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator activated receptor (PPAR) α and γ, G-protein coupled receptor (GPR) 120 and cyclooxygenase (COX)-2. Effective doses for each ω-3 PUFA are difficult to determine due to inconsistencies in dose and time of exposure between different in vitro models and between in vivo and in vitro models. Further research is needed to determine the anti-inflammatory potential of less-studied ω-3 PUFAs, including docosapentaenoic acid and stearidonic acid.
PubMed: 33478161
DOI: 10.3390/foods10010199 -
Arthritis Research & Therapy May 2015Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. Omega-3 (ω3) fatty acid supplementation has been associated with a...
Eicosapentaenoic acid and docosapentaenoic acid monoglycerides are more potent than docosahexaenoic acid monoglyceride to resolve inflammation in a rheumatoid arthritis model.
INTRODUCTION
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines and eicosanoids involved in RA pathogenesis. The aim of this study was to determine the therapeutic potential of ω3 monoglyceride (MAG-ω3) compounds in an in vivo rat model of RA induced by Complete Freund's Adjuvant (CFA).
METHOD
CFA rats were untreated or treated per os with three specific compounds, namely, MAG-docosahexaenoic acid (MAG-DHA), MAG-eicosapentaenoic acid (MAG-EPA) and MAG-docosapentaenoic acid (MAG-DPA). Morphological and histological analyses, as well as pro-inflammatory marker levels were determined following MAG-ω3 treatments.
RESULTS
Morphological and histological analyses revealed that MAG-EPA and MAG-DPA exhibited strong activity in reducing the progression and severity of arthritic disease in CFA rats. Following MAG-EPA and MAG-DPA treatments, plasma levels of the pro-inflammatory cytokines; interleukin 17A (IL-17A), IL-1β, IL-6 and tumor necrosis factor α (TNFα) were markedly lower when compared to CFA-untreated rats. Results also revealed a decreased activation of p38 mitogen-activated protein kinases (p38 MAPK) and nuclear factor-kappa B (NFκB) pathways correlated with a reduced expression of TNFα, cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2) and MMP-9 in paw homogenates derived from MAG-EPA and MAG-DPA-treated rats. Of interest, the combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in CFA rats.
CONCLUSION
Altogether, the present data suggest that MAG-EPA, without vitamin E, represents a new potential therapeutic strategy for resolving inflammation in arthritis.
Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Blotting, Western; Cyclooxygenase 2; Docosahexaenoic Acids; Eicosapentaenoic Acid; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Unsaturated; Female; Inflammation; Interleukin-17; Interleukin-1beta; Interleukin-6; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Monoglycerides; NF-kappa B; Rats, Inbred Lew; Severity of Illness Index; Tumor Necrosis Factor-alpha; p38 Mitogen-Activated Protein Kinases
PubMed: 26022389
DOI: 10.1186/s13075-015-0653-y -
BMC Musculoskeletal Disorders May 2024Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and...
BACKGROUND
Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and the key inflammatory mediators of synovium induced by different types of meniscal tears remain unclear.
METHODS
Magnetic resonance imaging (MRI) was employed to identify the type of meniscus tear, and the quantification of synovial inflammation was assessed through H&E staining assay. Transcription and expression levels of IL-1β and IL-6 were evaluated using bioinformatics, ELISA, RT-qPCR, and IHC of CD68 staining assays. The therapeutic potential of Docosapentaenoic Acid (DPA) was determined through network pharmacology, ELISA, and RT-qPCR assays. The safety of DPA was assessed using colony formation and EdU staining assays.
RESULTS
The results indicate that both IL-1β and IL-6 play pivotal roles in synovitis pathogenesis, with distinct expression levels across various subtypes. Among tested meniscus tears, oblique tear and bucket handle tear induced the most severe inflammation, followed by radial tear and longitudinal tear, while horizontal tear resulted in the least inflammation. Furthermore, in synovial inflammation induced by specific meniscus tears, the anterior medial tissues exhibited significantly higher local inflammation than the anterior lateral and suprapatellar regions, highlighting the clinical relevance and practical guidance of anterior medial tissues' inflammatory levels. Additionally, we identified the essential omega-3 fatty acid DPA as a potential therapeutic agent for synovitis, demonstrating efficacy in blocking the transcription and expression of IL-1β and IL-6 with minimal side effects.
CONCLUSION
These findings provide valuable insights into the nuanced nature of synovial inflammation induced by various meniscal tear classifications and contribute to the development of new adjunctive therapeutic agents in the management of synovitis.
Topics: Tibial Meniscus Injuries; Synovitis; Magnetic Resonance Imaging; Synovial Membrane; Humans; Fatty Acids, Unsaturated; Male; Interleukin-1beta; Animals; Interleukin-6; Female; Menisci, Tibial; Mice; Disease Models, Animal
PubMed: 38734632
DOI: 10.1186/s12891-024-07491-1 -
Frontiers in Immunology 2023Activation of pancreatic stellate cells (PSCs) to cancer-associated fibroblasts (CAFs) is responsible for the extensive desmoplastic reaction observed in PDAC stroma: a...
Activation of pancreatic stellate cells (PSCs) to cancer-associated fibroblasts (CAFs) is responsible for the extensive desmoplastic reaction observed in PDAC stroma: a key driver of pancreatic ductal adenocarcinoma (PDAC) chemoresistance leading to poor prognosis. Specialized pro-resolving mediators (SPMs) are prime modulators of inflammation and its resolution, traditionally thought to be produced by immune cells. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipid mediator profiling PSCs as well as primary human CAFs express enzymes and receptors to produce and respond to SPMs. Human PSC/CAF SPM secretion profile can be modulated by rendering these cells activated [transforming growth factor beta (TGF-β)] or quiescent [all- retinoic acid (ATRA)]. ATRA-induced nuclear translocation of arachidonate-15-lipoxygenase (ALOX15) was linked to increased production of n-3 docosapentaenoic acid-derived Resolvin D5 (RvD5), among other SPMs. Inhibition of RvD5 formation increases cancer cell invasion, whereas addback of this molecule reduced activated PSC-mediated cancer cell invasion. We also observed that circulating concentrations of RvD5 levels were decreased in peripheral blood of metastatic PDAC patients when compared with those measured in plasma of non-metastatic PDAC patients. Together, these findings indicate that RvD5 may regulate cancer-stroma cross-talk and invasion.
Topics: Humans; Arachidonate 15-Lipoxygenase; Pancreatic Stellate Cells; Chromatography, Liquid; Tandem Mass Spectrometry; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Tretinoin; Neoplasm Invasiveness
PubMed: 38035115
DOI: 10.3389/fimmu.2023.1248547 -
Environment International Mar 2024Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains...
Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (β = -0.18, 95%CI: -0.29 - -0.07, P = 0.002) and progressive motility (β = -0.27, 95%CI: -0.43 - -0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: β = 0.26, 95%CI: 0.01 - -0.51, P = 0.047; progressive motility: β = 0.64, 95%CI: 0.23 - 1.05, P = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.
Topics: Male; Humans; Semen; Semen Analysis; Endocrine Disruptors; Bayes Theorem; Spermatozoa; Fatty Acids, Omega-3; Benzophenones; Fatty Acids, Unsaturated
PubMed: 38471262
DOI: 10.1016/j.envint.2024.108571 -
American Journal of Physiology. Heart... Aug 2014n-3 Polyunsaturated fatty acids (n-3 PUFA) have been shown to reduce inflammation and proliferation of pulmonary artery smooth muscle cells under pathophysiological...
n-3 Polyunsaturated fatty acids (n-3 PUFA) have been shown to reduce inflammation and proliferation of pulmonary artery smooth muscle cells under pathophysiological conditions. However, the anti-inflammatory effect of the newly synthesized docosapentaenoic acid monoacylglyceride (MAG-DPA) on key signaling pathways in pulmonary hypertension (PH) pathogenesis has yet to be assessed. The aim of the present study was to determine the effects of MAG-DPA on pulmonary inflammation and remodeling occurring in a rat model of PH, induced by a single injection of monocrotaline (MCT: 60 mg/kg). Our results demonstrate that MAG-DPA treatment for 3 wk following MCT injection resulted in a significant improvement of right ventricular hypertrophy (RVH) and a reduction in Fulton's Index (FI). Morphometric analyses revealed that the wall thickness of pulmonary arterioles was significantly lower in MCT + MAG-DPA-treated rats compared with controls. This result was further correlated with a decrease in Ki-67 immunostaining. Following MAG-DPA treatments, lipid analysis showed a consistent increase in DPA together with lower levels of arachidonic acid (AA), as measured in blood and tissue samples. Furthermore, in MCT-treated rats, oral administration of MAG-DPA decreased NF-κB and p38 MAPK activation, leading to a reduction in MMP-2, MMP-9, and VEGF expression levels in lung tissue homogenates. Altogether, these data provide new evidence regarding the mode of action of MAG-DPA in the prevention of pulmonary hypertension induced by MCT.
Topics: Animals; Arachidonic Acid; Arterioles; Fatty Acids, Unsaturated; Hypertension, Pulmonary; Inflammation; Lipid Metabolism; Lung; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Monoglycerides; NF-kappa B; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A; Vascular Remodeling; p38 Mitogen-Activated Protein Kinases
PubMed: 24929859
DOI: 10.1152/ajpheart.00814.2013