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Cell Reports. Medicine Feb 2024Cold exposure activates brown adipose tissue (BAT) and potentially improves cardiometabolic health through the secretion of signaling lipids by BAT. Here, we show that...
Cold exposure activates brown adipose tissue (BAT) and potentially improves cardiometabolic health through the secretion of signaling lipids by BAT. Here, we show that 2 h of cold exposure in young adults increases the levels of omega-6 and omega-3 oxylipins, the endocannabinoids (eCBs) anandamide and docosahexaenoylethanolamine, and lysophospholipids containing polyunsaturated fatty acids. Contrarily, it decreases the levels of the eCBs 1-LG and 2-LG and 1-OG and 2-OG, lysophosphatidic acids, and lysophosphatidylethanolamines. Participants overweight or obese show smaller increases in omega-6 and omega-3 oxylipins levels compared to normal weight. We observe that only a small proportion (∼4% on average) of the cold-induced changes in the plasma signaling lipids are slightly correlated with BAT volume. However, cold-induced changes in omega-6 and omega-3 oxylipins are negatively correlated with adiposity, glucose homeostasis, lipid profile, and liver parameters. Lastly, a 24-week exercise-based randomized controlled trial does not modify plasma signaling lipid response to cold exposure.
Topics: Young Adult; Humans; Adipose Tissue, Brown; Oxylipins; Obesity; Fatty Acids, Omega-3; Cardiovascular Diseases
PubMed: 38262411
DOI: 10.1016/j.xcrm.2023.101387 -
Nature Communications May 2024The genomes of charophyte green algae, close relatives of land plants, typically do not show signs of developmental regulation by phytohormones. However, scattered...
The genomes of charophyte green algae, close relatives of land plants, typically do not show signs of developmental regulation by phytohormones. However, scattered reports of endogenous phytohormone production in these organisms exist. We performed a comprehensive analysis of multiple phytohormones in Viridiplantae, focusing mainly on charophytes. We show that auxin, salicylic acid, ethylene and tRNA-derived cytokinins including cis-zeatin are found ubiquitously in Viridiplantae. By contrast, land plants but not green algae contain the trans-zeatin type cytokinins as well as auxin and cytokinin conjugates. Charophytes occasionally produce jasmonates and abscisic acid, whereas the latter is detected consistently in land plants. Several phytohormones are excreted into the culture medium, including auxin by charophytes and cytokinins and salicylic acid by Viridiplantae in general. We note that the conservation of phytohormone biosynthesis and signaling pathways known from angiosperms does not match the capacity for phytohormone biosynthesis in Viridiplantae. Our phylogenetically guided analysis of established algal cultures provides an important insight into phytohormone biosynthesis and metabolism across Streptophyta.
Topics: Plant Growth Regulators; Indoleacetic Acids; Phylogeny; Cytokinins; Viridiplantae; Ethylenes; Oxylipins; Salicylic Acid; Abscisic Acid; Gene Expression Regulation, Plant; Cyclopentanes; Biological Evolution; Chlorophyta; Signal Transduction
PubMed: 38719800
DOI: 10.1038/s41467-024-47753-z -
Heliyon Jun 2024Exploring the symbiotic potential between fungal and yeast species, this study investigates the co-cultivation dynamics of , a prolific producer of pharmacologically...
Exploring the symbiotic potential between fungal and yeast species, this study investigates the co-cultivation dynamics of , a prolific producer of pharmacologically relevant secondary metabolites, and . The collaborative interaction between these microorganisms catalyzed a substantial elevation in the biosynthesis of secondary metabolites, prominently Monacolin K and natural pigments. Central to our discoveries was the identification and enhanced production of oxylipins (13S-hydroxyoctadecadienoic acid,13S-HODE), putative quorum-sensing molecules, within the co-culture environment. Augmentation with exogenous oxylipins not only boosted Monacolin K production by over half but also mirrored morphological adaptations in , affecting both spores and mycelial structures. This augmentation was paralleled by a significant upregulation in the transcriptional activity of genes integral to the Monacolin K biosynthetic pathway, as well as genes implicated in pigment and spore formation. Through elucidating the interconnected roles of quorum sensing, G-protein-coupled receptors, and the G-protein-mediate signaling pathway, this study provides a comprehensive view of the molecular underpinnings facilitating these metabolic enhancements. Collectively, our findings illuminate the profound influence of co-culture on , advocating for oxylipins as a pivotal quorum-sensing mechanism driving the observed symbiotic benefits.
PubMed: 38845857
DOI: 10.1016/j.heliyon.2024.e31619 -
Journal of Crohn's & Colitis Oct 2023Ulcerative colitis [UC] is a chronic disease with rising incidence and unclear aetiology. Deep molecular phenotyping by multiomics analyses may provide novel insights...
INTRODUCTION
Ulcerative colitis [UC] is a chronic disease with rising incidence and unclear aetiology. Deep molecular phenotyping by multiomics analyses may provide novel insights into disease processes and characteristic features of remission states.
METHODS
UC pathomechanisms were assessed by proteome profiling of human tissue specimens, obtained from five distinct colon locations for each of the 12 patients included in the study. Systemic disease-associated alterations were evaluated thanks to a cross-sectional setting of mass spectrometry-based multiomics analyses comprising proteins, metabolites, and eicosanoids of plasma obtained from UC patients during acute episodes and upon remission, in comparison with healthy controls.
RESULTS
Tissue proteome profiling indicated colitis-associated activation of neutrophils, macrophages, B and T cells, fibroblasts, endothelial cells and platelets, and hypoxic stress, and suggested a general downregulation of mitochondrial proteins accompanying the establishment of apparent wound healing-promoting activities including scar formation. Whereas pro-inflammatory proteins were apparently upregulated by immune cells, the colitis-associated epithelial cells, fibroblasts, endothelial cells, and platelets seemed to predominantly contribute anti-inflammatory and wound healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulations of gut and gut microbiome-derived metabolites. Upon remission several, but not all, molecular candidate biomarker levels recovered back to normal.
CONCLUSION
The findings may indicate that microvascular damage and platelet deregulation hardly resolve upon remission, but apparently persist as disease-associated molecular signatures. This study presents local and systemic molecular alterations integrated in a model for UC pathomechanisms, potentially supporting the assessment of disease and remission states in UC patients.
PubMed: 36961872
DOI: 10.1093/ecco-jcc/jjad052 -
Neuroscience and Biobehavioral Reviews Jul 2024Alzheimer's disease (AD) is prevalent around the world, yet our understanding of the disease is still very limited. Recent work suggests that the cornerstone of AD may... (Review)
Review
Alzheimer's disease (AD) is prevalent around the world, yet our understanding of the disease is still very limited. Recent work suggests that the cornerstone of AD may include the inflammation that accompanies it. Failure of a normal pro-inflammatory immune response to resolve may lead to persistent central inflammation that contributes to unsuccessful clearance of amyloid-beta plaques as they form, neuronal death, and ultimately cognitive decline. Individual metabolic, and dietary (lipid) profiles can differentially regulate this inflammatory process with aging, obesity, poor diet, early life stress and other inflammatory factors contributing to a greater risk of developing AD. Here, we integrate evidence for the interface between these factors, and how they contribute to a pro-inflammatory brain milieu. In particular, we discuss the importance of appropriate polyunsaturated fatty acids (PUFA) in the diet for the metabolism of specialised pro-resolving mediators (SPMs); raising the possibility for dietary strategies to improve AD outlook.
Topics: Alzheimer Disease; Humans; Aging; Animals; Neuroinflammatory Diseases; Inflammation; Brain
PubMed: 38762130
DOI: 10.1016/j.neubiorev.2024.105724 -
Clinical Nutrition (Edinburgh, Scotland) Jan 2024The relationship between lipid mediators and severe obesity remains unclear. Our study investigates the impact of severe obesity on plasma concentrations of oxylipins...
BACKGROUND
The relationship between lipid mediators and severe obesity remains unclear. Our study investigates the impact of severe obesity on plasma concentrations of oxylipins and fatty acids and explores the consequences of weight loss.
METHODS
In the clinical trial identifier NCT05554224 study, 116 patients with severe obesity and 63 overweight/obese healthy controls matched for age and sex (≈2:1) provided plasma. To assess the effect of surgically induced weight loss, we requested paired plasma samples from 44 patients undergoing laparoscopic sleeve gastrectomy one year after the procedure. Oxylipins were measured using ultra-high-pressure liquid chromatography coupled to a triple quadrupole mass spectrometer via semi-targeted lipidomics. Cytokines and markers of interorgan crosstalk were measured using enzyme-linked immunosorbent assays.
RESULTS
We observed significantly elevated levels of circulating fatty acids and oxylipins in patients with severe obesity compared to their metabolically healthier overweight/obese counterparts. Our findings indicated that sex and liver disease were not confounding factors, but we observed weak correlations in plasma with circulating adipokines, suggesting the influence of adipose tissue. Importantly, while weight loss restored the balance in circulating fatty acids, it did not fully normalize the oxylipin profile. Before surgery, oxylipins derived from lipoxygenase activity, such as 12-HETE, 11-HDoHE, 14-HDoHE, and 12-HEPE, were predominant. However, one year following laparoscopic sleeve gastrectomy, we observed a complex shift in the oxylipin profile, favoring species from the cyclooxygenase pathway, particularly proinflammatory prostanoids like TXB2, PGE2, PGD2, and 12-HHTrE. This transformation appears to be linked to a reduction in adiposity, underscoring the role of lipid turnover in the development of metabolic disorders associated with severe obesity.
CONCLUSIONS
Despite the reduction in fatty acid levels associated with weight loss, the oxylipin profile shifts towards a predominance of more proinflammatory species. These observations underscore the significance of seeking mechanistic approaches to address severe obesity and emphasize the importance of closely monitoring the metabolic adaptations after weight loss.
Topics: Humans; Fatty Acids; Obesity; Obesity, Morbid; Overweight; Oxylipins; Weight Loss
PubMed: 38101315
DOI: 10.1016/j.clnu.2023.12.002 -
Progress in Lipid Research Apr 2024Oxylipins are potent lipid mediators with increasing interest in clinical research. They are usually measured in systemic circulation and can provide a wealth of... (Review)
Review
Oxylipins are potent lipid mediators with increasing interest in clinical research. They are usually measured in systemic circulation and can provide a wealth of information regarding key biological processes such as inflammation, vascular tone, or blood coagulation. Although procedures still require harmonization to generate comparable oxylipin datasets, performing comprehensive profiling of circulating oxylipins in large studies is feasible and no longer restricted by technical barriers. However, it is essential to improve and facilitate the biological interpretation of complex oxylipin profiles to truly leverage their potential in clinical research. This requires regular updating of our knowledge about the metabolism and the mode of action of oxylipins, and consideration of all factors that may influence circulating oxylipin profiles independently of the studied disease or condition. This review aims to provide the readers with updated and necessary information regarding oxylipin metabolism, their different forms in systemic circulation, the current limitations in deducing oxylipin cellular effects from in vitro bioactivity studies, the biological and technical confounding factors needed to consider for a proper interpretation of oxylipin profiles.
PubMed: 38697517
DOI: 10.1016/j.plipres.2024.101276 -
Neurotrauma Reports 2023Currently approved blood biomarkers detect intracranial lesions in adult patients with mild to moderate traumatic brain injury (TBI) acutely post-injury. However, blood...
Levels of Arachidonic Acid-Derived Oxylipins and Anandamide Are Elevated Among Military ɛ4 Carriers With a History of Mild Traumatic Brain Injury and Post-Traumatic Stress Disorder Symptoms.
Currently approved blood biomarkers detect intracranial lesions in adult patients with mild to moderate traumatic brain injury (TBI) acutely post-injury. However, blood biomarkers are still needed to help with a differential diagnosis of mild TBI (mTBI) and post-traumatic stress disorder (PTSD) at chronic post-injury time points. Owing to the association between phospholipid (PL) dysfunction and chronic consequences of TBI, we hypothesized that examining bioactive PL metabolites (oxylipins and ethanolamides) would help identify long-term lipid changes associated with mTBI and PTSD. Lipid extracts of plasma from active-duty soldiers deployed to the Iraq/Afghanistan wars (control = 52, mTBI = 21, PTSD = 34, and TBI + PTSD = 13) were subjected to liquid chromatography/mass spectrometry analysis to examine oxylipins and ethanolamides. Linear regression analyses followed by comparisons were performed to assess the association of these lipids with diagnostic classifications. Significant differences were found in oxylipins derived from arachidonic acid (AA) between controls and mTBI, PTSD, and mTBI + PTSD groups. Levels of AA-derived oxylipins through the cytochrome P450 pathways and anandamide were significantly elevated among mTBI + PTSD patients who were carriers of the apolipoprotein E E4 allele. These studies demonstrate that AA-derived oxylipins and anandamide may be unique blood biomarkers of PTSD and mTBI + PTSD. Further, these AA metabolites may be indicative of an underlying inflammatory process that warrants further investigation. Future validation studies in larger cohorts are required to determine a potential application of this approach in providing a differential diagnosis of mTBI and PTSD in a clinical setting.
PubMed: 37786567
DOI: 10.1089/neur.2023.0045 -
Cancer Prevention Research... Nov 2023Aspirin and eicosapentaenoic acid (EPA) reduce colorectal adenomatous polyp risk and affect synthesis of oxylipins including prostaglandin E2. We investigated whether 35... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Aspirin and eicosapentaenoic acid (EPA) reduce colorectal adenomatous polyp risk and affect synthesis of oxylipins including prostaglandin E2. We investigated whether 35 SNPs in oxylipin metabolism genes such as cyclooxygenase (PTGS) and lipoxygenase (ALOX), as well as 7 SNPs already associated with colorectal cancer risk reduction by aspirin (e.g., TP53; rs104522), modified the effects of aspirin and EPA on colorectal polyp recurrence in the randomized 2 × 2 factorial seAFOod trial. Treatment effects were reported as the incidence rate ratio (IRR) and 95% confidence interval (CI) by stratifying negative binomial and Poisson regression analyses of colorectal polyp risk on SNP genotype. Statistical significance was reported with adjustment for the false discovery rate as the P and q value. 542 (of 707) trial participants had both genotype and colonoscopy outcome data. Reduction in colorectal polyp risk in aspirin users compared with nonaspirin users was restricted to rs4837960 (PTGS1) common homozygotes [IRR, 0.69; 95% confidence interval (CI), 0.53-0.90); q = 0.06], rs2745557 (PTGS2) compound heterozygote-rare homozygotes [IRR, 0.60 (0.41-0.88); q = 0.06], rs7090328 (ALOX5) rare homozygotes [IRR 0.27 (0.11-0.64); q = 0.05], rs2073438 (ALOX12) common homozygotes [IRR, 0.57 (0.41-0.80); q = 0.05], and rs104522 (TP53) rare homozygotes [IRR, 0.37 (0.17-0.79); q = 0.06]. No modification of colorectal polyp risk in EPA users was observed. In conclusion, genetic variants relevant to the proposed mechanism of action on oxylipins are associated with differential colorectal polyp risk reduction by aspirin in individuals who develop multiple colorectal polyps. SNP genotypes should be considered during development of personalized, predictive models of colorectal cancer chemoprevention by aspirin.
PREVENTION RELEVANCE
Single-nucleotide polymorphisms in genes controlling lipid mediator signaling may modify the colorectal polyp prevention activity of aspirin. Further investigation is required to determine whether testing for genetic variants can be used to target cancer chemoprevention by aspirin to those who will benefit most.
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Colonic Polyps; Colorectal Neoplasms; Cyclooxygenase 2; Eicosapentaenoic Acid; Genes, p53; Lipoxygenase; Oxylipins; Polymorphism, Single Nucleotide; Risk Reduction Behavior; Tumor Suppressor Protein p53
PubMed: 37756582
DOI: 10.1158/1940-6207.CAPR-23-0111 -
Marine Drugs Dec 2023Rheumatoid arthritis (RA) is an invalidating chronic autoimmune disorder characterized by joint inflammation and progressive bone damage. Dietary intervention is an... (Review)
Review
Rheumatoid arthritis (RA) is an invalidating chronic autoimmune disorder characterized by joint inflammation and progressive bone damage. Dietary intervention is an important component in the treatment of RA to mitigate oxidative stress, a major pathogenic driver of the disease. Alongside traditional sources of antioxidants, microalgae-a diverse group of photosynthetic prokaryotes and eukaryotes-are emerging as anti-inflammatory and immunomodulatory food supplements. Several species accumulate therapeutic metabolites-mainly lipids and pigments-which interfere in the pro-inflammatory pathways involved in RA and other chronic inflammatory conditions. The advancement of the clinical uses of microalgae requires the continuous exploration of phytoplankton biodiversity and chemodiversity, followed by the domestication of wild strains into reliable producers of said metabolites. In addition, the tractability of microalgal genomes offers unprecedented possibilities to establish photosynthetic microbes as light-driven biofactories of heterologous immunotherapeutics. Here, we review the evidence-based anti-inflammatory mechanisms of microalgal metabolites and provide a detailed coverage of the genetic engineering strategies to enhance the yields of endogenous compounds and to develop innovative bioproducts.
Topics: Humans; Microalgae; Arthritis, Rheumatoid; Antioxidants; Dietary Supplements; Anti-Inflammatory Agents
PubMed: 38132951
DOI: 10.3390/md21120630