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PloS One 2022Multiple factors in addition to over consumption lead to obesity and non-alcoholic fatty liver disease (NAFLD) in the United States and worldwide. CYP2B6 is the only...
Multiple factors in addition to over consumption lead to obesity and non-alcoholic fatty liver disease (NAFLD) in the United States and worldwide. CYP2B6 is the only human detoxification CYP whose loss is associated with obesity, and Cyp2b-null mice show greater diet-induced obesity with increased steatosis than wildtype mice. However, a putative mechanism has not been determined. LC-MS/MS revealed that CYP2B6 metabolizes PUFAs, with a preference for metabolism of ALA to 9-HOTrE and to a lesser extent 13-HOTrE with a preference for metabolism of PUFAs at the 9- and 13-positions. To further study the role of CYP2B6 in vivo, humanized-CYP2B6-transgenic (hCYP2B6-Tg) and Cyp2b-null mice were fed a 60% high-fat diet for 16 weeks. Compared to Cyp2b-null mice, hCYP2B6-Tg mice showed reduced weight gain and metabolic disease as measured by glucose tolerance tests, however hCYP2B6-Tg male mice showed increased liver triglycerides. Serum and liver oxylipin metabolite concentrations increased in male hCYP2B6-Tg mice, while only serum oxylipins increased in female hCYP2B6-Tg mice with the greatest increases in LA oxylipins metabolized at the 9 and 13-positions. Several of these oxylipins, specifically 9-HODE, 9-HOTrE, and 13-oxoODE, are PPAR agonists. RNA-seq data also demonstrated sexually dimorphic changes in gene expression related to nuclear receptor signaling, especially CAR > PPAR with qPCR suggesting PPARγ signaling is more likely than PPARα signaling in male mice. Overall, our data indicates that CYP2B6 is an anti-obesity enzyme, but probably to a lesser extent than murine Cyp2b's. Therefore, the inhibition of CYP2B6 by xenobiotics or dietary fats can exacerbate obesity and metabolic disease potentially through disrupted PUFA metabolism and the production of key lipid metabolites.
Topics: Humans; Male; Female; Mice; Animals; Oxylipins; Cytochrome P-450 CYP2B6; Chromatography, Liquid; Mice, Inbred C57BL; Tandem Mass Spectrometry; Obesity; Diet, High-Fat; Fatty Acids, Unsaturated; Liver; Non-alcoholic Fatty Liver Disease; PPAR alpha; Mice, Knockout; Fatty Acids
PubMed: 36520866
DOI: 10.1371/journal.pone.0277053 -
Arthritis Research & Therapy Jul 2021Oxylipins are biological lipids that have been implicated in inflammation. We previously found that certain oxylipins correlated with clinical manifestations in...
BACKGROUND
Oxylipins are biological lipids that have been implicated in inflammation. We previously found that certain oxylipins correlated with clinical manifestations in psoriatic arthritis (PsA) patients. Here, we compare oxylipin profiles in PsA patients and those with psoriasis (PsO) without inflammatory arthritis to identify oxylipins that associate with specific disease manifestations to better understand disease pathogenesis and identify new biomarkers.
METHODS
Consecutive patients with PsA (who met the CASPAR classification criteria for PsA) and PsO were recruited from the Rheumatology Outpatient Clinic. A thorough clinical examination was performed, including entheseal (Leeds enthesitis index (LEI)) and joint involvement (SJC/TJC 66/68). Patients were evaluated for pain and global disease activity on a visual analog scale (VAS) ranging from 0 to 100. This was followed by disease activity scores calculation: cDAPSA (Disease Activity Index for Psoriatic Arthritis) and Psoriasis Area and Severity Index (PASI). Serum oxylipins were determined by mass spectrometry and their association with clinical characteristics (PASI/LEI and cDAPSA) was analyzed using Metaboanalyst 4.0 and R version 3.6.1.
RESULTS
Twenty PsO (average age 52 [10.8], 55% males) and 19 PsA patients (average age 60.5 [11.4], 63.1% males) were included. PsO patients had an average body mass index (BMI) of 33.7 (6.84) and an average PASI of 3.8 (4.2). PsA patients had an average BMI of 31.9 (5.6), TJC of 9.3 (10.41), SJC of 3.7 (4.23), with an average cDAPSA of 23.3 (11.4). 63.1% of PsA patients had enthesitis (average LEI 2.2 [3]) and the same percentage had psoriasis (average PASI 3(5]). Sera were analyzed for oxylipin levels. PsO and PsA patients with higher PASI score (> 2.5) had significantly lower serum concentrations of pro-inflammatory oxylipins, most of them arachidonic acid derived (AA). Oxylipin profiling did not associate with cDAPSA. Interestingly, several AA-derived oxylipins (5,15 di-HETE (5S,15S-dihydroxy-6E,8Z,10Z,13E-eicosatetraenoic acid), 5-oxoETE (5-Oxo-eicosatetraenoic acid), PGE2 (prostaglandin E2), 11bPGE2 (11 beta prostaglandin D2), and LTB4 (leukotriene B4)) were significantly increased in PsA patients with enthesitis compared to those without.
CONCLUSIONS
The AA-derived proinflammatory oxylipins were lower in both PsO and PsA patients with higher skin scores. Joint disease activity was not associated with the concentrations of oxylipins. Yet, enthesitis was associated with an increase of AA-derived pro-inflammatory oxylipins in PsA patients. Further studies are needed to determine whether oxylipin profiling can be a good biomarker of enthesitis in PsA patients.
Topics: Arachidonic Acids; Arthritis, Psoriatic; Female; Humans; Male; Middle Aged; Oxylipins; Psoriasis; Severity of Illness Index
PubMed: 34303373
DOI: 10.1186/s13075-021-02575-y -
Comparative Biochemistry and... May 2024Chemical cues play important roles in mediating ecological interactions. Oxylipins, oxygenated metabolites of fatty acids, are one signalling molecule type that...
Chemical cues play important roles in mediating ecological interactions. Oxylipins, oxygenated metabolites of fatty acids, are one signalling molecule type that influences the physiology and function of species, suggesting their broader significance in chemical communication within aquatic systems. Yet, our current understanding of their function is restricted taxonomically and contextually making it difficult to infer their ecological significance. Snails and leeches are ubiquitous in freshwater ecosystems worldwide, yet little is known about their oxylipin profiles and the factors that cause their profiles to change. As snails and leeches differ taxonomically and represent different trophic groups, we postulated oxylipin profile differences. For snails, we hypothesized that ontogeny (non-reproductive vs reproductive) and predation (non-infested vs leech-infested) would affect oxylipin profiles. Oxylipins were characterized from water conditioned with the snail Planorbella duryi and leech Helobdella lineata, and included three treatment types (snails, leeches, and leech-infested snails) with the snails consisting of three size classes: small (5-6 mm, non-reproductive) and medium and large (13-14 and 19-20 mm, reproductive). The two species differed in the composition of their oxylipin profiles both in diversity and amounts. Further, ontogeny and predation affected the diversity of oxylipins emitted by snails. Our experimental profiles of oxylipins show that chemical cues within freshwater systems vary depending upon the species emitting the signals, the developmental stage of the species, as well as from ecological interactions such as predation. We also identified some candidates, like 9-HETE and PGE, that could be explored more directly for their physiological and ecological roles in freshwater systems.
Topics: Animals; Oxylipins; Ecosystem; Predatory Behavior; Snails; Fresh Water; Leeches
PubMed: 38360203
DOI: 10.1016/j.cbpa.2024.111607 -
Pain Dec 2020Chronic posttraumatic headache (PTH) is among the most common and disabling sequelae of traumatic brain injury (TBI). Current PTH treatments are often only partially...
Chronic posttraumatic headache (PTH) is among the most common and disabling sequelae of traumatic brain injury (TBI). Current PTH treatments are often only partially effective and have problematic side effects. We previously showed in a small randomized trial of patients with chronic nontraumatic headaches that manipulation of dietary fatty acids decreased headache frequency, severity, and pain medication use. Pain reduction was associated with alterations in oxylipins derived from n-3 and n-6 fatty acids, suggesting that oxylipins could potentially mediate clinical pain reduction. The objective of this study was to investigate whether circulating oxylipins measured in the acute setting after TBI could serve as prognostic biomarkers for developing chronic PTH. Participants enrolled in the Traumatic Head Injury Neuroimaging Classification Protocol provided serum within 3 days of TBI and were followed up at 90 days postinjury with a neurobehavioral symptom inventory (NSI) and satisfaction with life survey. Liquid chromatography-tandem mass spectrometry methods profiled 39 oxylipins derived from n-3 docosahexaenoic acid (DHA), and n-6 arachidonic acid and linoleic acid. Statistical analyses assessed the association of oxylipins with headache severity (primary outcome, measured by headache question on NSI) as well as associations between oxylipins and total NSI or satisfaction with life survey scores. Among oxylipins, 4-hydroxy-DHA and 19,20-epoxy-docosapentaenoate (DHA derivatives) were inversely associated with headache severity, and 11-hydroxy-9-epoxy-octadecenoate (a linoleic acid derivative) was positively associated with headache severity. These findings support a potential for DHA-derived oxylipins as prognostic biomarkers for development of chronic PTH.
Topics: Biomarkers; Docosahexaenoic Acids; Headache; Humans; Oxylipins; Prognosis
PubMed: 32694380
DOI: 10.1097/j.pain.0000000000001983 -
PloS One 2018Obesity-induced chronic inflammation is a key factor in type 2 diabetes. A vicious cycle involving pro-inflammatory mediators between adipocytes and macrophages is a...
Obesity-induced chronic inflammation is a key factor in type 2 diabetes. A vicious cycle involving pro-inflammatory mediators between adipocytes and macrophages is a common cause of chronic inflammation in the adipose tissue. Tomato is one of the most popular vegetables and is associated with a reduced risk of diabetes. However, the molecular mechanism underlying the effect of tomato on diabetes is unclear. In this study, we focused on anti-inflammatory compounds in tomato. We found that the extract of tomato reduced plasma glucose and inflammatory markers in mice. We screened anti-inflammatory fractions in tomato using lipopolysaccharide-stimulated RAW264.7 macrophages, and active compounds were estimated by liquid chromatography-mass spectrometry over a wide range. Surprisingly, a large number of compounds including oxylipin and coumarin derivatives were estimated as anti-inflammatory compounds. Especially, 9-oxo-octadecadienoic acid and daphnetin suppressed pro-inflammatory cytokines in RAW264.7 macrophages inhibiting mitogen-activated protein kinase phosphorylation and inhibitor of kappa B α protein degradation. These findings suggest that tomato containing diverse anti-inflammatory compounds ameliorates chronic inflammation in obese adipose tissue.
Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Blood Glucose; Chromatography, High Pressure Liquid; Coumarins; Cytokines; Drug Evaluation, Preclinical; Solanum lycopersicum; MAP Kinase Signaling System; Macrophages; Male; Mice; Mice, Inbred C57BL; Nitric Oxide; Obesity; Oxylipins; Plant Extracts; RAW 264.7 Cells; Spectrometry, Mass, Electrospray Ionization; Umbelliferones
PubMed: 29329333
DOI: 10.1371/journal.pone.0191203 -
Plant Biotechnology Journal Dec 2015Plants and their biotic enemies, such as microbial pathogens and herbivorous insects, are engaged in a desperate battle which would determine their survival-death fate.... (Review)
Review
Plants and their biotic enemies, such as microbial pathogens and herbivorous insects, are engaged in a desperate battle which would determine their survival-death fate. Plants have evolved efficient and sophisticated systems to defend against such attackers. In recent years, significant progress has been made towards a comprehensive understanding of inducible defence system mediated by jasmonate (JA), a vital plant hormone essential for plant defence responses and developmental processes. This review presents an overview of JA action in plant defences and discusses how microbial pathogens evade plant defence system through hijacking the JA pathway.
Topics: Cyclopentanes; Oxylipins; Plant Diseases; Plant Growth Regulators; Plant Immunity; Plant Physiological Phenomena; Symbiosis
PubMed: 26096226
DOI: 10.1111/pbi.12417 -
Cells Mar 2023Jasmonic acid (JA) and its derivatives, all named jasmonates, are the simplest phytohormones which regulate multifarious plant physiological processes including... (Review)
Review
Jasmonic acid (JA) and its derivatives, all named jasmonates, are the simplest phytohormones which regulate multifarious plant physiological processes including development, growth and defense responses to various abiotic and biotic stress factors. Moreover, jasmonate plays an important mediator's role during plant interactions with necrotrophic oomycetes and fungi. Over the last 20 years of research on physiology and genetics of plant JA-dependent responses to pathogens and herbivorous insects, beginning from the discovery of the JA co-receptor CORONATINE INSENSITIVE1 (COI1), research has speeded up in gathering new knowledge on the complexity of plant innate immunity signaling. It has been observed that biosynthesis and accumulation of jasmonates are induced specifically in plants resistant to necrotrophic fungi (and also hemibiotrophs) such as mostly investigated model ones, i.e., , or . However, it has to be emphasized that the activation of JA-dependent responses takes place also during susceptible interactions of plants with necrotrophic fungi. Nevertheless, many steps of JA function and signaling in plant resistance and susceptibility to necrotrophs still remain obscure. The purpose of this review is to highlight and summarize the main findings on selected steps of JA biosynthesis, perception and regulation in the context of plant defense responses to necrotrophic fungal pathogens.
Topics: Arabidopsis; Arabidopsis Proteins; Cyclopentanes; Oxylipins
PubMed: 37048100
DOI: 10.3390/cells12071027 -
International Journal of Molecular... Feb 2020Lipid-derived plant hormone jasmonates are implicated in plant growth, reproductive performance, senescence, secondary metabolite productions, and defense against both... (Review)
Review
Lipid-derived plant hormone jasmonates are implicated in plant growth, reproductive performance, senescence, secondary metabolite productions, and defense against both necrotrophic pathogens and feeding insects. A major jasmonate is (+)-7--jasmonoyl-l-isoleucine (JA-Ile), which is perceived by the unique COI1-JAZ coreceptor system. Recent advances in plant chemical biology have greatly informed the bioscience of jasmonate, including the development of chemical tools such as the antagonist COR-MO; the agonist NOPh; and newly developed jasmonates, including JA-Ile-macrolactone and 12-OH-JA-Ile. This review article summarizes the current status of plant chemical biology as it pertains to jasmonates, and offers some perspectives for the future.
Topics: Arabidopsis; Arabidopsis Proteins; Cyclopentanes; Oxylipins; Plant Proteins; Protein Binding; Receptors, Cell Surface; Repressor Proteins
PubMed: 32046227
DOI: 10.3390/ijms21031124 -
Arthritis & Rheumatology (Hoboken, N.J.) Mar 2021Eicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are...
OBJECTIVE
Eicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are linked to rheumatoid arthritis (RA), suggesting that metabolization is enhanced, the role of oxylipins in disease stratification remains unexplored. This study was undertaken to characterize oxylipin networks during the earliest stages of RA and evaluate their associations with clinical features and treatment outcomes.
METHODS
In total, 60 patients with early RA (according to the American College of Rheumatology/European League Against Rheumatism 2010 criteria), 11 individuals with clinically suspect arthralgia (CSA), and 28 healthy control subjects were recruited. Serum samples were collected at the time of onset. In the early RA group, 50 patients who had not been exposed to disease-modifying antirheumatic drug (DMARD) or glucocorticoid treatment at the time of recruitment were prospectively followed up at 6 and 12 months after having received conventional synthetic DMARDs. A total of 75 oxylipins, mostly derived from arachidonic, eicosapentanoic, and linoleic acids, were identified in the serum by liquid chromatography tandem mass spectrometry.
RESULTS
Univariate analyses demonstrated differences in expression patterns of 14 oxylipins across the RA, CSA, and healthy control groups, with each exhibiting a different trajectory. Network analyses revealed a strong grouping pattern of oxylipins in RA patients, whereas in individuals with CSA, a fuzzy network of oxylipins with higher degree and closeness was found. Partial least-squares discriminant analyses yielded variable important projection scores of >1 for 22 oxylipins, which allowed the identification of 2 clusters. Cluster usage differed among the groups (P = 0.003), and showed associations with disease severity and low rates of remission at 6 and 12 months in RA patients who were initially treatment-naive. Pathway enrichment analyses revealed different precursors and pathways between the groups, highlighting the relevance of the arachidonic acid pathway in individuals with CSA and the lipooxygenase pathway in patients with early RA. In applying distinct oxylipin signatures, subsets of seropositive and seronegative RA could be identified.
CONCLUSION
Oxylipin networks differ across stages during the earliest phases of RA. These distinct oxylipin networks could potentially elucidate pathways with clinical relevance for disease progression, clinical heterogeneity, and treatment response.
Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Case-Control Studies; Discriminant Analysis; Disease Progression; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Oxylipins
PubMed: 33001576
DOI: 10.1002/art.41537 -
The Plant Cell Jun 2019
Topics: Cyclopentanes; Solanum lycopersicum; Medicago sativa; Oxylipins; Plant Growth Regulators; Nicotiana
PubMed: 31048334
DOI: 10.1105/tpc.19.00333