Search Results (307)

The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies before and after weight loss. Using mass spectrometry, 275 lipid species were analysed in non-obese controls, patients with severe obesity, and patients one year after bariatric surgery. The results showed that severe obesity disrupts lipid pathways, contributing to lipotoxicity, inflammation, mitochondrial stress, and abnormal lipid metabolism. Although weight loss improved these disturbances, surgery did not fully normalise the lipid profiles of all patients. Outcomes varied depending on their baseline liver health and genetic differences. Persistent alterations in cholesterol handling, membrane composition, and mitochondrial function were observed in partial responders. Elevated levels of sterol lipids, glycerophospholipids, and sphingolipids emerged as markers of complete metabolic recovery, identifying candidates for targeted post-surgical interventions. These findings support the use of lipidomics to personalise obesity treatment and follow-up. Full article

Background/Objectives: Oxylipins, a family of oxygenated natural products derived from polyunsaturated fatty acids (PUFAs), play crucial roles in various physiological processes. Evaluating their levels in vivo helps to reveal their roles in health and disease. Because of the numerous isomers of oxylipins, it is essential to develop efficient and precise analytical methods for their identification and quantification. The objective of this study is to establish a quantitative method for oxylipin analysis and its application to the assessment of oxylipins in children’s plasma, with potential implications for diagnostic use in pediatric populations. Methods: A liquid chromatography–electrospray ionization–tandem mass spectrometry method was developed to quantify 64 oxylipins and four precursor PUFAs within 36 min. The limits of quantification ranged from 0.25 to 50 pg, with most analytes showing recoveries and matrix effects between 85 and 110% and between 90 and 110%, respectively. Intra- and inter-day precision values were within 15%. The established method was applied to plasma samples from children aged 9–12 years (boys = 181; girls = 161) in Hokkaido, Japan, to assess the relation between plasma oxylipin and PUFA levels and age, sex, and body mass index. Results: There was no significant correlation between oxylipin levels and age, sex, or body mass index. However, among the PUFAs, boys had higher eicosapentaenoic acid and arachidonic acid levels than those of girls, with a significant increase in eicosapentaenoic acid levels in the overweight group compared with those in the underweight group. Conclusions: We successfully developed a simple and highly selective method for the analysis of oxylipins in preadolescent children’s plasma samples. Thus, this study provides a foundation for broader application of the developed method to different biological samples in future studies. Full article

Caleosin/peroxygenases (CLO/PXGs) play critical functional roles during plant development, oxylipin metabolism, and the response to abiotic/biotic stressors and environmental toxins. In Oryza sativa, peroxygenase-9 (OsPXG9) catabolizes intermediates in oxylipin biosynthesis produced by lipoxygenase-9 (9-LOX) and scavenges HOOH and CuOOH by transferring oxygen to hydroxy fatty acids (HFAs) but not to the free fatty acids. The resulting epoxide derivatives of HFAs are then enzymatically or non-enzymatically hydrolyzed into the corresponding trihydroxy derivatives. Results presented here demonstrate OsPXG9′s specificity for catabolizing products of the 9-LOX (and not for the 13-LOX) pathway of oxylipin biosynthesis. Overexpression of OsPXG9 reduces ROS (reactive oxygen species) abundance and reduces drought- and salt-stress-induced apoptotic cell death. The high expression level of OsPXG9 also stimulates drought- and salt-induced but not basal expression of antioxidant enzymes/pathways in plants, thereby increasing cellular resistance to drought. These results suggest that OsPXG9 decreases ROS abundance and is essential to increase resilience in rice plants exposed to exogenous or endogenous abiotic stress. Full article

Background/Objectives: High-fat-diet (HFD) consumption drives chronic liver injury via gut dysbiosis and metabolic disturban. Apple cider vinegar, rich in polyphenols and organic acids, shows potential in metabolic regulation. This study aimed to investigate whether apple cider vinegar powder (ACVP) alleviates HFD-induced liver injury by modulating the gut–liver axis. Methods: For 12 weeks, C57BL/6 J mice received daily ACVP gavage while being fed a HFD. A series of biological assessments were conducted, including systemic metabolic evaluations (body weight, serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), and lipid/glucose levels), hepatic steatosis (hematoxylin and eosin (H&E) staining), intestinal microbiome characterization (16S rRNA gene genomic analysis), and comprehensive metabolite profiling of cecal contents (non-targeted metabolomics). Pearson correlation networks integrated multi-omics data. Results: ACVP attenuated HFD-induced weight gain by 26.3%, hepatomegaly and dyslipidemia, as well as reduced hepatic lipid vacuoles and serum ALT (48%)/AST (21.5%). ACVP restored gut microbiota diversity, enriching Muribaculaceae. Cecal metabolomics identified 38 HFD-perturbed metabolites reversed by ACVP, including indolelactate, hyocholate, and taurocholic acid. the Kyoto encyclopedia of genes and genomes (KEGG) analysis revealed ACVP-mediated recovery of linoleic acid metabolism. Correlation networks linked Akkermansia to anti-inflammatory metabolites (e.g., trans-ferulic), while Desulfobacterota correlated with pro-inflammatory oxylipins (e.g., 12,13-dihydroxy-9Z-octadecenoic acid (DHOME)). Conclusions: ACVP mitigates HFD-induced liver injury by remodeling gut microbiota, restoring microbial metabolites, and enhancing gut–liver crosstalk. Full article

C₁₇-polyacetylenic (PA) oxylipins are bioactive compounds in carrots (Daucus carota L.) with structurally unique features and diverse biological roles. These PA-derived compounds have garnered attention for their potential contributions to human health, particularly in cancer prevention and anti-inflammatory applications. This trade-off between health benefits and sensory quality underscores the importance of understanding the genetic and biochemical basis of PA biosynthesis, as it may allow for the development of carrots with optimized levels of these compounds that balance both nutritional and sensory qualities. In this review, we seek biochemically inspired strategies to elucidate the complexities of PA-derived oxylipins biosynthesis in carrots, a topic that remains largely unexplored. By integrating current knowledge on polyacetylene biology, biosynthesis, genetic and enzymatic factors involved in their production and the implications for enhancing the medicinal value of carrots we aim to provide a foundation for future research that could unlock the full potential of carrots as a source of health-promoting bioactive compounds. Full article

Inflammation is a complicated physiological process that contributes to a variety of disorders including osteoarthritis (OA) and rheumatoid arthritis (RA). Endocannabinoids and the endocannabinoid system (ECS) play a pivotal role in the physiological response to pain and inflammation. A clinical study to investigate the role of the endocannabinoid system and related lipids in pain and inflammation in OA and RA was performed. In total, 80 subjects, namely, 25 patients with RA, 18 with OA, and 37 healthy participants, were included. Sixteen endocannabinoids and congeners, as well as 129 oxylipins, were quantified in plasma using specific, quantitative LC-MS/MS assays. The endocannabinoid analysis revealed significantly lower levels of 2-arachidonoylglycerol (2-AG) in RA and OA patients compared to healthy participants. In contrast, the EC levels of the ethanolamide group (anandamide, docosahexaenoyl-EA, palmitoleoyl-EA, and other ethanolamides) were higher in the RA study cohort and to a lesser extent also in the OA cohort. This analysis of oxylipins revealed lower levels of the pro-resolving lipid 9-oxo-octadecadienoic acid (9-oxoODE) and the ω-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in RA compared to all other study cohorts. 2-AG is a key regulator of nociception and inflammation, and its relatively low levels might be a mechanistic contributor to residual pain and inflammation in RA and OA. Several changes in pro- and anti-inflammatory lipid mediators were detected, including lower levels of EPA and DHA in RA, which might reveal the potential for nutritional supplementation with these anti-inflammatory fatty acids. Full article

Systemic molecular responses to pathogen-associated molecular patterns and their modulation by antioxidants are poorly understood in humans. Here, we present a two-stage clinical interventional study in healthy humans challenged with lipopolysaccharide. In the first step, the kinetics of inflammatory modulators within 8 h were investigated by plasma proteomics and lipidomics. In a second step, the effects of a placebo-controlled antioxidant intervention on the individual responses prior to another lipopolysaccharide challenge were determined. Plasma proteomics revealed an early involvement of the endothelium and platelets, followed by the induction of liver-derived acute phase proteins and an innate immune cell response. Untargeted lipidomics revealed an early release of fatty acids and taurocholic acid, followed by complex regulatory events exerted by oxylipins. The consistent lipopolysaccharide-induced downregulation of lysophospholipids suggested the involvement of the Lands cycle, and the downregulation of deoxycholic acid reinforced emerging links between the inflammasome and bile acids. Groups of molecules with similar kinetics to lipopolysaccharide challenge were observed to share precursors, synthesizing enzymes or cellular origin. Dietary antioxidant supplementation prior to lipopolysaccharide challenge had no detectable effect on protein kinetics but significantly downregulated pro-inflammatory sphingosine-1-phosphate and increased levels of oxylipins, 20-HEPE, and 22-HDoHE, which have been described to facilitate the resolution of inflammation. The present study identified a complex network of lipid mediators deregulated in plasma upon lipopolysaccharide challenge and highlighted the role of platelets, endothelial cells, and erythrocytes as potential inflammatory modulators. While dietary antioxidant supplementation hardly affected the initiation of inflammation, it may exert its effects supporting the resolution of inflammation. Full article

The present study provides a detailed review of cardiovascular biomarkers critical for the diagnosis, prognosis, and pathophysiology of cardiovascular diseases, the leading cause of global morbidity and mortality. These biomarkers aid in detecting disease onset, progression, and therapeutic responses, providing insights into molecular mechanisms. Enzyme markers like AST, CK-MB, LDH, CA-III, and HBDH are pivotal for detecting myocardial injury during acute events. Protein markers such as CRP, H-FABP, and MPO shed light on inflammation and oxidative stress. Cardiac Troponins, the gold standard for myocardial infarction diagnosis, exhibit high specificity and sensitivity, while IMA and GPBB indicate ischemia and early myocardial damage. Peptide markers, including BNP and NT-proBNP, are crucial for heart failure diagnosis and management, reflecting ventricular stress and remodeling. Novel peptides like MR-proANP and MR-proADM aid in assessing disease severity. Lipid markers such as lipoprotein-associated phospholipase A2 and oxylipins provide insights into lipid metabolism and atherosclerosis. Inflammatory and stress-related biomarkers, including TNFα, IL-6, GDF-15, and Pentraxin 3, illuminate chronic inflammation in CVDs. Hormonal markers like copeptin and endothelin-1 highlight neurohormonal activation, while emerging markers such as ST2, galectin-3, PAPP-A, and TMAO elucidate fibrosis, remodeling, and metabolic dysregulation. The inclusion of microRNAs and long non-coding RNAs represents a breakthrough in biomarker research, offering sensitive tools for early detection, risk stratification, and therapeutic targeting. This review emphasizes the diagnostic and prognostic utility of these biomarkers, advancing cardiovascular care through personalized medicine. Full article

Nineteen potential mimics of 8,9-epoxyeicosatrienoic acid (8,9-EET), a natural bioactive oxylipin, were synthesized and evaluated for their ability to protect renal mesangial cells against sorafenib-induced cell death in a water-soluble tetrazolium (WST-8) assay. All compounds were also evaluated as inhibitors of soluble epoxide hydrolase. As expected of a potent pan-kinase inhibitor the drug sorafenib caused a significant decrease in cell viability in HRMCs. Several analogs containing amide and oxamide groups in place of the epoxide showed efficacy in reducing sorafenib induced human renal mesangial cell (HRMC) death. Oxamide containing analogs proved particularly effective, with the most promising analog increasing cell viability five-fold over control at 1 µM. These analogs, containing an oxamide group as a bioisostere for the epoxide in 8,9-EET, did not display significant inhibitory activity towards soluble epoxide hydrolase. This preliminary structure–activity relationship analysis reveals the oxamide group as a promising bioisostere for the epoxide in the 8,9-position of the fatty acid chain, producing protective effects against sorafenib-induced cell death in HRMCs. Collectively, these findings demonstrate the potential for using epoxide mimics and particularly oxamides as 8,9-EET analogs as bioisosteres of the corresponding epoxide in a therapeutic strategy against sorafenib-induced glomerular nephrotoxicity. Full article

Salinity is one of the main abiotic stresses that limits plant growth. This study addressed how the composition and diversity of root-associated bacterial communities reacts over time to salt-induced stress conditions. To understand its adaptation to soil salinization, the microbiome was studied by total DNA extraction and sequencing, using the Illumina MiSeq platform. Additionally, we evaluated the plant metabolites associated with salt stress (oxylipins, fatty acids (FAs) and hormones) by mass spectrometry. Salinity reduced rhizosphere bacterial diversity in salt-treated plants at 7 and 14 days and triggered a progressive shift of the bacterial structure, starting 7 days after salt stress imposed. The bacterial rhizosphere community became enriched with specific bacteria associated with potential genes involved in the PGP trait and ion homeostasis. For these plants, metabolites that showed higher levels included 9-lipoxygenase (LOX) oxylipins, which were found at days 7 and 14. The results indicated that salinity seems to have induced changes in the rhizosphere bacterial community, with characteristics that may help the plant respond to the imposed stress. Furthermore, our study highlighted the role of 9-LOX oxylipins in responding to salinity stress, providing new insights into the complex plant–microbe interactions under salt stress. Full article

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting inflammation and PUFAs mitigating it. Oxylipins, bioactive molecules derived from the oxidation of PUFAs, play crucial roles in immune regulation across various organisms, including plants, fungi, and bacteria. These molecules, such as prostaglandins, leukotrienes, and resolvins, regulate immune responses during infection and inflammation. The production of oxylipins extends beyond mammals, with fungi and bacteria synthesizing these molecules to modulate immune responses, promoting both defense and pathogenesis. This review delves into the multifaceted effects of oxylipins, exploring their impact on host and microbial interactions, with a focus on their potential for therapeutic applications in modulating infection and immune response. Full article

Background: Astrocytes play a key role in the inflammatory process accompanying various neurological diseases. Extracellular ATP accompanies inflammatory processes in the brain, but its effect on lipid mediators (oxylipins) in astrocytes remains elusive. Metformin is a hypoglycemic drug with an anti-inflammatory effect that has been actively investigated in the context of therapy for neuroinflammation, but its mechanisms of action are not fully elucidated. Therefore, we aimed to characterize the effects of ATP on inflammatory markers and oxylipin profiles; determine the dependence of these effects on the adaptation of astrocytes to high glucose levels; and evaluate the possibility of modulating ATP effects using metformin. Methods: We estimated the ATP-mediated response of primary rat astrocytes cultured at normal (NG, 5 mM) and high (HG, 22.5 mM) glucose concentrations for 48 h before stimulation. Cell responses were assessed by monitoring changes in the expression of inflammatory markers (TNFα, IL-6, IL-10, IL-1β, iNOS, and COX-2) and the synthesis of oxylipins (41 compounds), assayed with ultra-high-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). Intracellular pathways were assessed by analyzing the phosphorylation of p38; ERK MAPK; transcription factors STAT3 and NF-κB; and the enzymes mediating oxylipin synthesis, COX-1 and cPLA2. Results: The stimulation of cells with ATP does not affect the expression of pro-inflammatory markers, increases the activities of p38 and ERK MAPKs, and activates oxylipin synthesis, shifting the profiles toward an increase in anti-inflammatory compounds (PGD2, PGA2, 12-HHT, and 18-HEPE). The ATP effects are reduced in HG astrocytes. Metformin potentiated ATP-induced oxylipin synthesis (11-HETE, PGD2, 12-HHT, 15-HETE, 13-HDoHE, and 15-HETrE), which was predominantly evident in NG cells. Conclusions: Our data provide new evidence showing that ATP induces the release of anti-inflammatory oxylipins, and metformin enhances these effects. These results should be considered in the development of anti-inflammatory therapeutic approaches aimed at modulating astrocyte function in various pathologies. Full article

A new oxylipin (1) was isolated from cyanobacteria collected at Tokyo Bay, Japan. The structure of 1 was elucidated based on spectroscopic data including 1D and 2D NMR, as well as high-resolution mass spectrometry. The structure of 1 was elucidated to be (S)-2-hydroxy-3-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)propyl (E)-8-hydroperoxyhexadec-6-enoate. Full article

Cyp1b1 substantially affects hepatic vascular and stellate cells (HSC) with linkage to liver fibrosis. Despite minimal hepatocyte expression, Cyp1b1 deletion substantially impacts liver gene expression at birth and weaning. The appreciable Cyp1b1 expression in surrounding embryo mesenchyme, during early organogenesis, provides a likely source for Cyp1b1. Here defined breeder diets established major interconnected effects on neonatal liver of α-linolenic acid (ALA), vitamin A deficiency (VAD) and suboptimal iron fed mice. At birth Cyp1b1 deletion and VAD each activated perinatal HSC, while suppressing iron control by hepcidin. Cyp1b1 deletion also advanced the expression of diverse genes linked to iron regulation. Postnatal stimulations of Srebp-regulated genes in the fatty acid and cholesterol biosynthesis pathways were suppressed by Cyp1b1-deficiency. LncRNA H19 and the neutrophil alarmin S100a9 expression increased due to slower postnatal decline with Cyp1b1 deficiency. VAD reversed each of Cyp1b1 effect, probably due to enhanced HSC release of Apo-Rbp4. At birth, Cyp1b1 deletion enhanced H19 participation. Notably, a suppressor (Cnot3) decreased while an activity partner (Ezh2/H3K methylation) increased H19 expression. ALA elevated hepcidin mRNA and countered the inhibitory effects of Cyp1b1 deletion on hepcidin expression. Oxylipin metabolites of ALA from highly expressed hepatic Cyps are potential mediators. Cyp expression patterns demonstrated female dimorphism for neonatal liver. Mothers followed one of three fetal growth support programs probably linked to maturity at conception. Full article

The synergistic optimization of yield and abiotic/biotic resistance is of great significance in plant breeding. However, the genomic mechanisms underlying the selection for environmental adaptation and yield-related traits remain poorly understood. In this study, we identified a thaumatin-like protein (TLP), AtTLP1b, which was shown to pleiotropically regulate seed oil content and resistance to Sclerotinia sclerotiorum by gene knockout and overexpressing experiments in Arabidopsis. The oil composition oleic acid (C18:1), linoleic acid (C18:2), linolenic acid (C18:3) and eicosenoic acid (C20:1) were altered significantly in overexpressing and knockout lines. RNA-seq analysis revealed that overexpression of AtTLP1b significantly downregulated the expression levels of genes involved in wax, suberin synthesis, oxylipin metabolism and plant–pathogen interaction. Furthermore, more than half of the genes involved in the circadian rhythm–plant pathway were differentially expressed in the overexpressing lines. We propose that AtTLP1b primarily inhibits fatty acid synthesis and plant immune responses via the circadian rhythm–plant pathway. Our findings suggest that AtTLP1b plays a vital role in simultaneous improvement of seed oil content and resistance to S. sclerotiorum and provides a valuable resource for molecular breeding. Full article