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International Journal of Molecular... Mar 2023α-linolenic acid (ALA) is an essential C-18 n-3 polyunsaturated fatty acid (PUFA), which can be elongated to longer n-3 PUFAs, such as eicosapentaenoic acid (EPA).... (Review)
Review
α-linolenic acid (ALA) is an essential C-18 n-3 polyunsaturated fatty acid (PUFA), which can be elongated to longer n-3 PUFAs, such as eicosapentaenoic acid (EPA). These long-chain n-3 PUFAs have anti-inflammatory and pro-resolution effects either directly or through their oxylipin metabolites. However, there is evidence that the conversion of ALA to the long-chain PUFAs is limited. On the other hand, there is evidence in humans that supplementation of ALA in the diet is associated with an improved lipid profile, a reduction in the inflammatory biomarker C-reactive protein (CRP) and a reduction in cardiovascular diseases (CVDs) and all-cause mortality. Studies investigating the cellular mechanism for these beneficial effects showed that ALA is metabolized to oxylipins through the Lipoxygenase (LOX), the Cyclooxygenase (COX) and the Cytochrome P450 (CYP450) pathways, leading to hydroperoxy-, epoxy-, mono- and dihydroxylated oxylipins. In several mouse and cell models, it has been shown that ALA and some of its oxylipins, including 9- and 13-hydroxy-octadecatrienoic acids (9-HOTrE and 13-HOTrE), have immunomodulating effects. Taken together, the current literature suggests a beneficial role for diets rich in ALA in human CVDs, however, it is not always clear whether the described effects are attributable to ALA, its oxylipins or other substances present in the supplemented diets.
Topics: Humans; Mice; Animals; Oxylipins; alpha-Linolenic Acid; Cardiovascular Diseases; Eicosapentaenoic Acid; Diet; Fatty Acids, Omega-3
PubMed: 37047085
DOI: 10.3390/ijms24076110 -
EBioMedicine Nov 2022Fatty acid-derived lipid mediators including oxylipins, endocannabinoids (eCBs), and their analogues, have emerged as key metabolites in the inflammatory and immune... (Randomized Controlled Trial)
Randomized Controlled Trial
Acute and long-term exercise differently modulate plasma levels of oxylipins, endocannabinoids, and their analogues in young sedentary adults: A sub-study and secondary analyses from the ACTIBATE randomized controlled-trial.
BACKGROUND
Fatty acid-derived lipid mediators including oxylipins, endocannabinoids (eCBs), and their analogues, have emerged as key metabolites in the inflammatory and immune response to physiological stressors.
METHODS
This report was based on a sub-study and secondary analyses the ACTIBATE single-center unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129). The study was performed in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada. Eligible participants were young, sedentary adults with no chronic diseases. Here, we performed both an acute endurance and resistance exercise sub-studies (n.ß=.ß14 and 17 respectively), and a 24-week supervised exercise intervention, combining endurance and resistance exercise training at moderate-intensity (MOD-EX) or vigorous-intensity (VIG-EX) exercise groups, in young sedentary adults. Randomization was performed by unrestricted randomization. Plasma levels of oxylipins, eCBs, and their analogues were measured using liquid chromatography-tandem mass spectrometry.
FINDINGS
Both endurance and resistance exercise increased by.ß+50% the plasma levels of dihomo-..-linolenic acid and arachidonic acid (AA) omega-6 derived oxylipins, as well as eicosapentaenoic acid and docosahexaenoic acid omega-3 derived after 3 and 120.ßmin of the bout of exercise (all ...ß....ß0.219 and P.ß..±.ß0.039). These exercise modalities also increased the levels of anandamide and eCBs analogues (+25%). 145 young sedentary adults were assigned to a control (CON, n.ß=.ß54), a MOD-EX (n.ß=.ß48) or a VIG-EX (n.ß=.ß43). 102 participants were included in the final long-term analyses (CON, n.ß=.ß36; MOD-EX, n.ß=.ß33; and VIG-EX, n.ß=.ß33) of the trial. After 24-week of supervised exercise, MOD-EX decreased plasma levels of omega-6 oxylipins, concretely linoleic acid (LA) and adrenic acid derived oxylipins, and the eCBs analogues OEA and LEA in comparison to the CON (all P.ß..±.ß0.021). VIG-EX decreased LA-derived oxylipins and LEA compared to CON. No relevant adverse events were recorded.
INTERPRETATION
Endurance and resistance exercises acutely increased plasma levels of oxylipins, eCBs, and their analogues, whereas 24 weeks of exercise training decreased fasting plasma levels of omega-6 oxylipins, and eCBs analogues in young, sedentary adults.
FUNDING
See Acknowledgments section.
Topics: Humans; Adult; Oxylipins; Endocannabinoids; Eicosapentaenoic Acid; Docosahexaenoic Acids; Exercise
PubMed: 36374769
DOI: 10.1016/j.ebiom.2022.104313 -
Molecular Plant May 2017
Topics: Arabidopsis; Arabidopsis Proteins; Biological Transport; Cyclopentanes; Membrane Transport Proteins; Oxylipins; Nicotiana
PubMed: 28365333
DOI: 10.1016/j.molp.2017.03.007 -
The Journal of Pain Mar 2021Oxylipins are lipid peroxidation products that participate in nociceptive, inflammatory, and vascular responses to injury. Effects of oxylipins depend on tissue-specific...
Oxylipins are lipid peroxidation products that participate in nociceptive, inflammatory, and vascular responses to injury. Effects of oxylipins depend on tissue-specific differences in accumulation of precursor polyunsaturated fatty acids and the expression of specific enzymes to transform the precursors. The study of oxylipins in nociception has presented technical challenges leading to critical knowledge gaps in the way these molecules operate in nociception. We applied a systems-based approach to characterize oxylipin precursor fatty acids, and expression of genes coding for proteins involved in biosynthesis, transport, signaling and inactivation of pro- and antinociceptive oxylipins in pain circuit tissues. We further linked these pathways to nociception by demonstrating intraplantar carrageenan injection induced gene expression changes in oxylipin biosynthetic pathways. We determined functional-biochemical relevance of the proposed pathways in rat hind paw and dorsal spinal cord by measuring basal and stimulated levels of oxylipins throughout the time-course of carrageenan-induced inflammation. Finally, when oxylipins were administered by intradermal injection we observed modulation of nociceptive thermal hypersensitivity, providing a functional-behavioral link between oxylipins, their molecular biosynthetic pathways, and involvement in pain and nociception. Together, these findings advance our understanding of molecular lipidomic systems linking oxylipins and their precursors to nociceptive and inflammatory signaling pathways in rats. PERSPECTIVE: We applied a systems approach to characterize molecular pathways linking precursor lipids and oxylipins to nociceptive signaling. This systematic, quantitative evaluation of the molecular pathways linking oxylipins to nociception provides a framework for future basic and clinical research investigating the role of oxylipins in pain.
Topics: Animals; Carrageenan; Disease Models, Animal; Gas Chromatography-Mass Spectrometry; Gene Expression; Hyperalgesia; Lipidomics; Male; Nociception; Oxylipins; Rats; Rats, Sprague-Dawley; Sequence Analysis, RNA; Signal Transduction; Transcriptome
PubMed: 33031942
DOI: 10.1016/j.jpain.2020.09.001 -
Free Radical Biology & Medicine Nov 2019Oxylipins, including the well-known eicosanoids, are potent lipid mediators involved in numerous physiological and pathological processes. Therefore, their quantitative... (Review)
Review
Oxylipins, including the well-known eicosanoids, are potent lipid mediators involved in numerous physiological and pathological processes. Therefore, their quantitative profiling has gained a lot of attention during the last years notably in the active field of health biomarker discovery. Oxylipins include hundreds of structurally and stereochemically distinct lipid species which today are most commonly analyzed by (ultra) high performance liquid chromatography-mass spectrometry based ((U)HPLC-MS) methods. To maximize the utility of oxylipin profiling in clinical research, it is crucial to understand and assess the factors contributing to the analytical and biological variability of oxylipin profiles in humans. In this review, these factors and their impacts are summarized and discussed, providing a framework for recommendations expected to enhance the interlaboratory comparability and biological interpretation of oxylipin profiling in clinical research.
Topics: Arachidonic Acid; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Eicosanoids; Fatty Acids, Unsaturated; Humans; Inflammation; Metabolomics; Neurodegenerative Diseases; Observer Variation; Oxylipins; Reproducibility of Results; Tandem Mass Spectrometry; Vasoconstriction; Vasodilation
PubMed: 31085232
DOI: 10.1016/j.freeradbiomed.2019.05.012 -
Pediatric Research May 2021Oxylipins are formed from oxidation of omega-6 (n6) and omega-3 (n3) fatty acids (FAs). Evidence for inflammatory effects comes mostly from adults.
BACKGROUND
Oxylipins are formed from oxidation of omega-6 (n6) and omega-3 (n3) fatty acids (FAs). Evidence for inflammatory effects comes mostly from adults.
METHODS
Oxylipins from n6 FA (27 n6-oxylipins) and n3 FA (12 n3-oxylipins) were measured through ultra-high-performance liquid chromatography-mass spectrometry (LC-MS/MS) in plasma from 111 children at risk of type 1 diabetes (age 1-17 years) studied longitudinally. Oxylipin precursor FAs (arachidonic acid, linoleic acid, alpha-linolenic acid, docosahexaenoic acid, eicosapentaenoic acid) were measured in red blood cell (RBC) membrane and plasma. Precursor FAs dietary intake was measured through food frequency questionnaire and environmental tobacco smoke (ETS) through questionnaires. Linear mixed models were used to test oxylipins with predictors.
RESULTS
Age associated with 15 n6- and 6 n3-oxylipins; race/ethnicity associated with 3 n6- and 1 n3-oxylipins; sex associated with 2 n6-oxylipins. ETS associated with lipoxin-A4. Oxylipins associated with precursor FAs in plasma more often than RBC. RBC levels and dietary intake of precursor FAs more consistently associated with n3-oxylipins than with n6-oxylipins.
CONCLUSIONS
In healthy children, oxylipin levels change with age. Oxylipins associated with precursor FAs more often in plasma than RBC or diet, suggesting that inflammatory regulation leading to FA release into plasma may also be a determinant of oxylipin generation.
IMPACT
This is the first study to examine predictors of oxylipins in healthy children at risk of type 1 diabetes. In healthy children at risk of type 1 diabetes, many oxylipins change with age, and most oxylipins do not differ by sex or race/ethnicity. Environmental tobacco smoke exposure was associated with the presence of lipoxin A4. Omega-6- and omega-3-related oxylipin levels were consistently associated with their respective precursor fatty acid levels measured in the plasma. Proportionally more omega-3 compared to omega-6 oxylipins were associated with dietary intake and red blood cell membrane levels of the respective precursor fatty acid.
Topics: Adolescent; Child; Child, Preschool; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Infant; Male; Oxylipins; Pediatrics
PubMed: 32726799
DOI: 10.1038/s41390-020-1084-2 -
American Journal of Physiology. Heart... Nov 2017Oxylipins are a group of fatty acid metabolites generated via oxygenation of polyunsaturated fatty acids and are involved in processes such as inflammation, immunity,... (Review)
Review
Oxylipins are a group of fatty acid metabolites generated via oxygenation of polyunsaturated fatty acids and are involved in processes such as inflammation, immunity, pain, vascular tone, and coagulation. As a result, oxylipins have been implicated in many conditions characterized by these processes, including cardiovascular disease and aging. The best characterized oxylipins in relation to cardiovascular disease are derived from the ω-6 fatty acid arachidonic acid. These oxylipins generally increase inflammation, hypertension, and platelet aggregation, although not universally. Similarly, oxylipins derived from the ω-6 fatty acid linoleic acid generally have more adverse than beneficial cardiovascular effects. Alternatively, most oxylipins derived from 20- and 22-carbon ω-3 fatty acids have anti-inflammatory, antiaggregatory, and vasodilatory effects that help explain the cardioprotective effects of these fatty acids. Much less is known regarding the oxylipins derived from the 18-carbon ω-3 fatty acid α-linolenic acid, but clinical trials with flaxseed supplementation have indicated that these oxylipins can have positive effects on blood pressure. Normal aging also is associated with changes in oxylipin levels in the brain, vasculature, and other tissues, indicating that oxylipin changes with aging may be involved in age-related changes in these tissues. A small number of trials in humans and animals with interventions that contain either 18-carbon or 20- and 22-carbon ω-3 fatty acids have indicated that dietary-induced changes in oxylipins may be beneficial in slowing the changes associated with normal aging. In summary, oxylipins are an important group of molecules amenable to dietary manipulation to target cardiovascular disease and age-related degeneration. Oxylipins are an important group of fatty acid metabolites amenable to dietary manipulation. Because of the role they play in cardiovascular disease and in age-related degeneration, oxylipins are gaining recognition as viable targets for specific dietary interventions focused on manipulating oxylipin composition to control these biological processes.
Topics: Aging; Animals; Arachidonic Acid; Cardiovascular Diseases; Diet; Fatty Acids, Omega-6; Humans; Oxylipins
PubMed: 28801523
DOI: 10.1152/ajpheart.00201.2017 -
Journal of Molecular Medicine (Berlin,... Jun 2017In mammals, three major oxygenases, cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYP450), generate an assortment of unique lipid mediators... (Review)
Review
In mammals, three major oxygenases, cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYP450), generate an assortment of unique lipid mediators (oxylipins) from polyunsaturated fatty acids (PUFAs) which exhibit pro- or anti-thrombotic activity. Over the years, novel oxylipins generated from the interplay of theoxygenase activity in various cells, such as the specialized pro-resolving mediators (SPMs), have been identified and investigated in inflammatory disease models. Although platelets have been implicated in inflammation, the role and mechanism of these SPMs produced from immune cells on platelet function are still unclear. This review highlights the burgeoning classes of oxylipins that have been found to regulate platelet function; however, their mechanism of action still remains to be elucidated.
Topics: Animals; Blood Platelets; Cytochrome P-450 Enzyme System; Humans; Lipoxygenase; Oxylipins; Prostaglandin-Endoperoxide Synthases
PubMed: 28528513
DOI: 10.1007/s00109-017-1542-4 -
Journal of Experimental Botany Mar 2017Plants synthesize jasmonates (JAs) in response to developmental cues or environmental stresses, in order to coordinate plant growth, development or defense against... (Review)
Review
Plants synthesize jasmonates (JAs) in response to developmental cues or environmental stresses, in order to coordinate plant growth, development or defense against pathogens and herbivores. Perception of pathogen or herbivore attack promotes synthesis of jasmonoyl-L-isoleucine (JA-Ile), which binds to the COI1-JAZ receptor, triggering the degradation of JAZ repressors and induction of transcriptional reprogramming associated with plant defense. Interestingly, some virulent pathogens have evolved various strategies to manipulate JA signaling to facilitate their exploitation of plant hosts. In this review, we focus on recent advances in understanding the mechanism underlying the enigmatic switch between transcriptional repression and hormone-dependent transcriptional activation of JA signaling. We also discuss various strategies used by pathogens and insects to manipulate JA signaling and how interfering with this could be used as a novel means of disease control.
Topics: Animals; Cyclopentanes; Food Chain; Gene Expression Regulation, Plant; Herbivory; Insecta; Oxylipins; Plant Growth Regulators; Plant Physiological Phenomena; Plants; Signal Transduction
PubMed: 28069779
DOI: 10.1093/jxb/erw478 -
Journal of Experimental Botany Feb 2023The phytohormone jasmonate is an essential endogenous signal in the regulation of multiple plant processes for environmental adaptation, such as primary root growth... (Review)
Review
The phytohormone jasmonate is an essential endogenous signal in the regulation of multiple plant processes for environmental adaptation, such as primary root growth inhibition and root hair elongation. Perception of environmental stresses promotes the accumulation of jasmonate, which is sensed by the CORONATINE INSENSITIVE1 (COI1)-JASMONATE ZIM-DOMAIN (JAZ) co-receptor, triggering the degradation of JAZ repressors and induction of transcriptional reprogramming. The basic helix-loop-helix (bHLH) subgroup IIIe transcription factors MYC2, MYC3, and MYC4 are the most extensively characterized JAZ-binding factors and together stimulate jasmonate-signaled primary root growth inhibition. Conversely, the bHLH subgroup IIId transcription factors (i.e. bHLH3 and bHLH17) physically associate with JAZ proteins and suppress jasmonate-induced root growth inhibition. For root hair development, JAZ proteins interact with and inhibit ROOT HAIR DEFECTIVE 6 (RHD6) and RHD6 LIKE1 (RSL1) transcription factors to modulate jasmonate-enhanced root hair elongation. Moreover, jasmonate also interacts with other signaling pathways (such as ethylene and auxin) to regulate primary root growth and/or root hair elongation. Here, we review recent progress into jasmonate-mediated primary root growth and root hair development.
Topics: Arabidopsis; Arabidopsis Proteins; Transcription Factors; Basic Helix-Loop-Helix Transcription Factors; Cyclopentanes; Oxylipins; Gene Expression Regulation, Plant
PubMed: 36346644
DOI: 10.1093/jxb/erac441