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Acta Pharmacologica Sinica Jul 2018Globally, cardiovascular diseases (CVDs) are the number one cause of mortality. Approximately 18 million people died from CVDs in 2015, representing more than 30% of all... (Review)
Review
Globally, cardiovascular diseases (CVDs) are the number one cause of mortality. Approximately 18 million people died from CVDs in 2015, representing more than 30% of all global deaths. New diagnostic tools and therapies are eagerly required to decrease the prevalence of CVDs related to mortality and/or risk factors leading to CVDs. Oxylipins are a group of metabolites, generated via oxygenation of polyunsaturated fatty acids that are involved in inflammation, immunity, and vascular functions, etc. Thus far, over 100 oxylipins have been identified, and have overlapping and interconnected roles. Important CVD pathologies such as hyperlipidemia, hypertension, thrombosis, hemostasis and diabetes have been linked to abnormal oxylipin signaling. Oxylipins represent a new era of risk markers and/or therapeutic targets in several diseases including CVDs. The role of many oxylipins in the progression or regression in CVD, however, is still not fully understood. An increased knowledge of the role of these oxygenated polyunsaturated fatty acids in cardiovascular dysfunctions or CVDs including hypertension could possibly lead to the development of biomarkers for the detection and their treatment in the future.
Topics: Animals; Cardiovascular Diseases; Humans; Oxylipins
PubMed: 29877318
DOI: 10.1038/aps.2018.24 -
The FEBS Journal Apr 2011In nearly every living organism, metabolites derived from lipid peroxidation, the so-called oxylipins, are involved in regulating developmental processes as well as... (Review)
Review
In nearly every living organism, metabolites derived from lipid peroxidation, the so-called oxylipins, are involved in regulating developmental processes as well as environmental responses. Among these bioactive lipids, the mammalian and plant oxylipins are the best characterized, and much information about their physiological role and biosynthetic pathways has accumulated during recent years. Although the occurrence of oxylipins and enzymes involved in their biosynthesis has been studied for nearly three decades, knowledge about fungal oxylipins is still scarce as compared with the situation in plants and mammals. However, the research performed so far has shown that the structural diversity of oxylipins produced by fungi is high and, furthermore, that the enzymes involved in oxylipin metabolism are diverse and often exhibit unusual catalytic activities. The aim of this review is to present a synopsis of the oxylipins identified so far in fungi and the enzymes involved in their biosynthesis.
Topics: Animals; Fungal Proteins; Fungi; Host-Pathogen Interactions; Lipid Peroxidation; Molecular Structure; Oxylipins; Plants
PubMed: 21281447
DOI: 10.1111/j.1742-4658.2011.08027.x -
Plant Signaling & Behavior 2014The production of free oxylipins in plants is exquisitely controlled by cellular mechanisms that respond to environmental factors such as mechanical damage, insect...
The production of free oxylipins in plants is exquisitely controlled by cellular mechanisms that respond to environmental factors such as mechanical damage, insect herbivory and pathogen infection. One of the main targets of these cellular mechanisms are glycerolipases class A (GLA); acyl-hydrolyzing enzymes that upon their biochemical activation release unsaturated fatty acids or acylated oxylipins from glycerolipids. Recent studies performed in the wild tobacco species Nicotiana attenuata have started to reveal the complexity and specificity of GLA-regulated free oxylipin production. I present a model in which individual GLA lipases associate with individual lipoxygenases (LOX) in chloroplast membranes and envelope to define the initial committed steps of distinct oxylipin biosynthesis pathways. The unravelling of the mechanisms that activate GLAs and LOXs at the biochemical level and that control the interaction between these enzymes and their association with membranes will prove to be fundamental to understand how plants control free oxylipin biogenesis.
Topics: Chloroplasts; Lipase; Lipid Metabolism; Lipoxygenases; Models, Biological; Oxylipins; Plants
PubMed: 24603593
DOI: 10.4161/psb.28429 -
Frontiers in Immunology 2022Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-organ inflammation and defect, which is linked to many molecule mediators. Oxylipins as a...
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-organ inflammation and defect, which is linked to many molecule mediators. Oxylipins as a class of lipid mediator have not been broadly investigated in SLE. Here, we applied targeted mass spectrometry analysis to screen the alteration of oxylipins in serum of 98 SLE patients and 106 healthy controls. The correlation of oxylipins to lupus nephritis (LN) and SLE disease activity, and the biomarkers for SLE classification, were analyzed. Among 128 oxylipins analyzed, 92 were absolutely quantified and 26 were significantly changed. They were mainly generated from the metabolism of several polyunsaturated fatty acids, including arachidonic acid (AA), linoleic acid (LA), docosahexanoic acid (DHA), eicosapentanoic acid (EPA) and dihomo-γ-linolenic acid (DGLA). Several oxylipins, especially those produced from AA, showed different abundance between patients with and without lupus nephritis (LN). The DGLA metabolic activity and DGLA generated PGE1, were significantly associated with SLE disease activity. Random forest-based machine learning identified a 5-oxylipin combination as potential biomarker for SLE classification with high accuracy. Seven individual oxylipin biomarkers were also identified with good performance in distinguishing SLE patients from healthy controls (individual AUC > 0.7). Interestingly, the biomarkers for differentiating SLE patients from healthy controls are distinct from the oxylipins differentially expressed in LN patients non-LN patients. This study provides possibilities for the understanding of SLE characteristics and the development of new tools for SLE classification.
Topics: Humans; Lupus Nephritis; Oxylipins; 8,11,14-Eicosatrienoic Acid; Eicosapentaenoic Acid; Alprostadil; Lupus Erythematosus, Systemic; Biomarkers; Arachidonic Acids; Linoleic Acids
PubMed: 36275708
DOI: 10.3389/fimmu.2022.964901 -
Molecular Plant Jan 2023Phytohormones integrate external environmental and developmental signals with internal cellular responses for plant survival and multiplication in changing surroundings.... (Review)
Review
Phytohormones integrate external environmental and developmental signals with internal cellular responses for plant survival and multiplication in changing surroundings. Jasmonate (JA), which might originate from prokaryotes and benefit plant terrestrial adaptation, is a vital phytohormone that regulates diverse developmental processes and defense responses against various environmental stresses. In this review, we first provide an overview of ligand-receptor binding techniques used for the characterization of phytohormone-receptor interactions, then introduce the identification of the receptor COI1 and active JA molecules, and finally summarize recent advances on the regulation of JA perception and its evolution.
Topics: Plant Growth Regulators; Arabidopsis Proteins; Ligands; Cyclopentanes; Oxylipins; Plants; Perception; Gene Expression Regulation, Plant
PubMed: 36056561
DOI: 10.1016/j.molp.2022.08.011 -
Pharmacology & Therapeutics Nov 2022Inflammation and oxidative stress play major roles in healthy and pathological pregnancy. Environmental exposure to chemical pollutants may adversely affect maternal and... (Review)
Review
Inflammation and oxidative stress play major roles in healthy and pathological pregnancy. Environmental exposure to chemical pollutants may adversely affect maternal and fetal health in pregnancy by dysregulating these critical underlying processes of inflammation and oxidative stress. Oxylipins are bioactive lipids that play a major role in regulating inflammation and increasing lines of evidence point towards an importance in pregnancy. The biosynthetic production of oxylipins requires oxygenation of polyunsaturated fatty acids, which can occur through several well-characterized enzymatic and nonenzymatic pathways. This review describes the state of the science of epidemiologic evidence on oxylipin production in pregnancy and its association with 1) key pregnancy outcomes and 2) environmental exposures. We searched PubMed for studies of pregnancy that measured one or more oxylipin analytes during pregnancy or delivery. We evaluated oxylipin associations with three categories of adverse pregnancy outcomes, including preeclampsia, preterm birth, and fetal growth restriction, along with several categories of environmental pollutants. The majority of studies evaluated one to two oxylipins, most of which focused on oxylipins produced from nonenzymatic processes of oxidative stress. However, an increasing number of recent studies have leveraged technological advancements to profile a large number of oxylipins produced from distinct biosynthetic pathways. Although the literature indicated robust evidence that oxylipins produced via nonenzymatic pathways are associated with pregnancy outcomes and environmental exposures, evidence for enzymatically produced oxylipins showed that associations may differ between biosynthetic pathways. Along with summarizing this evidence, we review promising therapeutic options to regulate oxylipin production and provide a set of recommendations for future epidemiologic studies in these research areas. Further evidence is needed to improve our understanding of how oxylipins may act as key biological mediators for the adverse effects of environmental pollutants on pregnancy outcomes.
Topics: Pregnancy; Female; Humans; Infant, Newborn; Oxylipins; Premature Birth; Environmental Exposure; Inflammation; Oxidative Stress; Environmental Pollutants
PubMed: 35367517
DOI: 10.1016/j.pharmthera.2022.108181 -
International Journal of Molecular... May 2024Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, ranking as the third most malignant. The incidence of CRC has been increasing with time, and it... (Review)
Review
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, ranking as the third most malignant. The incidence of CRC has been increasing with time, and it is reported that Westernized diet and lifestyle play a significant role in its higher incidence and rapid progression. The intake of high amounts of omega-6 ( - 6) PUFAs and low levels of omega-3 ( - 3) PUFAs has an important role in chronic inflammation and cancer progression, which could be associated with the increase in CRC prevalence. Oxylipins generated from PUFAs are bioactive lipid mediators and have various functions, especially in inflammation and proliferation. Carcinogenesis is often a consequence of chronic inflammation, and evidence has shown the particular involvement of - 6 PUFA arachidonic acid-derived oxylipins in CRC, which is further described in this review. A deeper understanding of the role and metabolism of PUFAs by their modifying enzymes, their pathways, and the corresponding oxylipins may allow us to identify new approaches to employ oxylipin-associated immunomodulation to enhance immunotherapy in cancer. This paper summarizes oxylipins identified in the context of the initiation, development, and metastasis of CRC. We further explore CRC chemo-prevention strategies that involve oxylipins as potential therapeutics.
Topics: Humans; Colorectal Neoplasms; Oxylipins; Inflammation; Animals; Fatty Acids, Omega-6
PubMed: 38791445
DOI: 10.3390/ijms25105408 -
Advances in Nutrition (Bethesda, Md.) Sep 2016Alzheimer disease (AD) is becoming one of the most prevalent neurodegenerative conditions worldwide. Although the disease progression is becoming better understood,... (Review)
Review
Alzheimer disease (AD) is becoming one of the most prevalent neurodegenerative conditions worldwide. Although the disease progression is becoming better understood, current medical interventions can only ameliorate some of the symptoms but cannot slow disease progression. Neuroinflammation plays an important role in the advancement of this disorder, and n-3 (ω-3) polyunsaturated fatty acids (PUFAs) are involved in both the reduction in and resolution of inflammation. These effects may be mediated by the anti-inflammatory and proresolving effects of bioactive lipid mediators (oxylipins) derived from n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in fish oil. Although interventions have generally used fish oil containing both EPA and DHA, several studies that used either EPA or DHA alone or specific oxylipins derived from these fatty acids indicate that they have distinct effects. Both DHA and EPA can reduce neuroinflammation and cognitive decline, but EPA positively influences mood disorders, whereas DHA maintains normal brain structure. Fewer studies with a plant-derived n-3 PUFA, α-linolenic acid, suggest that other n-3 PUFAs and their oxylipins also may positively affect AD. Further research identifying the unique anti-inflammatory and proresolving properties of oxylipins from individual n-3 PUFAs will enable the discovery of novel disease-management strategies in AD.
Topics: Alzheimer Disease; Anti-Inflammatory Agents; Brain; Cognition Disorders; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Inflammation; Mood Disorders; Oxylipins; alpha-Linolenic Acid
PubMed: 27633106
DOI: 10.3945/an.116.012187 -
Marine Drugs Jan 2016Marine algae are rich and heterogeneous sources of great chemical diversity, among which oxylipins are a well-recognized class of natural products. Algal oxylipins... (Review)
Review
Marine algae are rich and heterogeneous sources of great chemical diversity, among which oxylipins are a well-recognized class of natural products. Algal oxylipins comprise an assortment of oxygenated, halogenated, and unsaturated functional groups and also several carbocycles, varying in ring size and position in lipid chain. Besides the discovery of structurally diverse oxylipins in macroalgae, research has recently deciphered the role of some of these metabolites in the defense and innate immunity of photosynthetic marine organisms. This review is an attempt to comprehensively cover the available literature on the chemistry, biosynthesis, ecology, and potential bioactivity of oxylipins from marine macroalgae. For a better understanding, enzymatic and nonenzymatic routes were separated; however, both processes often occur concomitantly and may influence each other, even producing structurally related molecules.
Topics: Humans; Oxylipins; Seawater; Seaweed; Structure-Activity Relationship
PubMed: 26805855
DOI: 10.3390/md14010023 -
Scientific Reports Jul 2023This study determined if 18 days of supplementation with blueberries (BL) compared to placebo (PL) could mitigate muscle soreness and damage and improve inflammation... (Randomized Controlled Trial)
Randomized Controlled Trial
This study determined if 18 days of supplementation with blueberries (BL) compared to placebo (PL) could mitigate muscle soreness and damage and improve inflammation resolution in untrained adults (n = 49, ages 18-50 years) after engaging in a 90-min bout of "weekend warrior" eccentric exercise. The BL freeze dried supplement provided 1 cup of fresh blueberries per day equivalent with 805 mg/day total phenolics and 280 mg/day anthocyanins. Urine levels of eight BL gut-derived phenolics increased after 14- and 18-days supplementation with 83% higher concentrations in BL vs. PL (p < 0.001). The 90-min exercise bout caused significant muscle soreness and damage during 4d of recovery and a decrease in exercise performance with no significant differences between PL and BL. Plasma oxylipins were identified (n = 76) and grouped by fatty acid substrates and enzyme systems. Linoleic acid (LA) oxylipins generated from cytochrome P450 (CYP) (9,10-, 12,13-dihydroxy-9Z-octadecenoic acids) (diHOMEs) were lower in BL vs. PL (treatment effect, p = 0.051). A compositive variable of 9 plasma hydroxydocosahexaenoic acids (HDoHEs) generated from docosahexaenoic acid (DHA, 22:6) and lipoxygenase (LOX) was significantly higher in BL vs. PL (treatment effect, p = 0.008). The composite variable of plasma 14-HDoHE, 17-HDoHE, and the eicosapentaenoic acid (EPA)-derived oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE) (specialized pro-resolving lipid mediators, SPM, intermediates) was significantly higher in BL vs PL (treatment effect, p = 0.014). Pearson correlations showed positive relationships between post-exercise DHA-LOX HDoHEs and SPM intermediates with urine blueberry gut-derived phenolics (r = 0.324, p = 0.023, and r = 0.349, p = 0.015, respectively). These data indicate that 18d intake of 1 cup/day blueberries compared to PL was linked to a reduction in pro-inflammatory diHOMES and sustained elevations in DHA- and EPA-derived anti-inflammatory oxylipins in response to a 90-min bout of unaccustomed exercise by untrained adults.
Topics: Adult; Humans; Oxylipins; Anthocyanins; Blueberry Plants; Myalgia; Anti-Inflammatory Agents; Docosahexaenoic Acids; Eicosapentaenoic Acid
PubMed: 37488250
DOI: 10.1038/s41598-023-39269-1