GNPS - A Class of Anti-inflammatory Lipids Decrease with Aging in the Central Nervous System
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive Plus
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Alan Saghatelian
PROVIDER: MSV000090179 | GNPS | Mon Aug 22 16:54:00 BST 2022
REPOSITORIES: GNPS
Similar Datasets
Project description:Untargeted lipidomics of brain and spinal cord samples from female mice at 4, 12, 25, 48, and 78 weeks of age
2022-08-22 | MSV000090179 | MassIVE
Project description:Lipids contribute to the structure, development, and function of healthy brains. Dysregulated lipid metabolism is linked to aging and diseased brains. However, our understanding of lipid metabolism in aging brains remains limited. Here we examined the brain lipidome of mice across their lifespan using untargeted lipidomics. Co-expression network analysis highlighted a progressive decrease in 3-sulfogalactosyl diacylglycerols (SGDGs) and SGDG pathway members, including the potential degradation products lyso-SGDGs. SGDGs show an age-related decline specifically in the central nervous system and are associated with myelination. We also found that an SGDG dramatically suppresses LPS-induced gene expression and release of pro-inflammatory cytokines from macrophages and microglia by acting on the NF-κB pathway. The detection of SGDGs in human and macaque brains establishes their evolutionary conservation. This work enhances interest in SGDGs regarding their roles in aging and inflammatory diseases and highlights the complexity of the brain lipidome and potential biological functions in aging.
| S-EPMC9898107 | biostudies-literature
Project description:Increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice. FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g., palmitic-acid-9-hydroxy-stearic-acid, 9-PAHSA). PAHSAs are synthesized in vivo and regulated by fasting and high-fat feeding. PAHSA levels correlate highly with insulin sensitivity and are reduced in adipose tissue and serum of insulin-resistant humans. PAHSA administration in mice lowers ambient glycemia and improves glucose tolerance while stimulating GLP-1 and insulin secretion. PAHSAs also reduce adipose tissue inflammation. In adipocytes, PAHSAs signal through GPR120 to enhance insulin-stimulated glucose uptake. Thus, FAHFAs are endogenous lipids with the potential to treat type 2 diabetes.
| S-EPMC4260972 | biostudies-literature
Project description:Mice brain at different age were digested and cell suspension were prepared. Cells were stained using anti-CD45, F4/80, CD11b and Ly6C and sorted using an cell sorter BD ARIA. Macrophages were then prepared in order to perform single cell RNA-Seq
2022-08-08 | GSE198531 | GEO
Project description:Three hitherto undescribed Stemona alkaloids, named stemajapines A-C (1-3), along with six known alkaloids (4-9), were isolated and identified from the roots of Stemona japonica (Blume) Miq. (Stemonaceae). Their structures were established by the analysis of the mass data, NMR spectra, and computational chemistry. Stemjapines A and B were degraded maistemonines without spiro-lactone ring and skeletal methyl from maistemonine. Concurrence of alkaloids 1 and 2 revealed an undescribed way to form diverse Stemona alkaloids. Bioassay results disclosed the anti-inflammatory natural constituents stemjapines A and C with IC50 values of 19.7 and 13.8 µM, respectively, compared to positive control dexamethasone with 11.7 µM. The findings may point out a new direction of Stemona alkaloids inaddition to its traditional antitussive and insecticide activities.
| S-EPMC10011249 | biostudies-literature
Project description:Gene expression profiles were assessed in the hippocampus (HC), entorhinal cortex (EC), superior frontal gyrus (SG), and postcentral gyrus (PCG) across the lifespan of 63 cognitively intact individuals from 20-99 years old. New perspectives on the global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age (20-59 vs. 60-99) in the superior frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the 6th-7th decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident across the lifespan, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with downregulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with more widespread activation in the female brain. These data open new opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain, and suggest that this balance is set differently in males and females, an intriguing and novel idea. HgU133plus2.0 microarray chips were used to profile gene expression in 4 brain regions of cognitively intact humans, across the adult lifespan (ages 20-99). Experiment Overall Design: Postmortem brain tissue was collected from ADRC brain banks. Cases were preferentially selected where 3 or more brain regions were available.
2008-10-26 | E-GEOD-11882 | biostudies-arrayexpress
Project description:In a paradigm shift, cancer research efforts are being dedicated to the discovery of chemopreventive agents. The goal of this approach is to delay or prevent the progression of augmented cell division to established cancer. Research has focused on dietary supplements, drugs, and endogenous lipids that possess anti-inflammatory properties. We undertook a lipidomics analysis of potential endogenous anti-inflammatory/anti-proliferative lipids in human plasma. We performed high-resolution mass spectrometric lipidomics analyses of plasma samples from controls and patients with colorectal, kidney, pancreatic, glioblastoma, and breast cancers. We present evidence that endogenous very-long-chain dicarboxylic acids (VLCDCA) are anti-inflammatory lipids that possess chemopreventative properties. In a family of VLCDCAs, we characterized VLCDCA 28:4, which is decreased in the plasma of patients with colorectal, kidney, and pancreatic cancers. The structure of this biomarker was validated by derivatization strategies, synthesis of the analytical standard, and tandem mass spectrometry. Our data suggest that VLCDCA 28:4 may be a useful blood biomarker for a number of cancers and that resupplying this lipid, via a prodrug for example, may offer a new anti-inflammatory therapeutic strategy for delaying or preventing the progression of cancer and other inflammatory diseases.
| S-EPMC6315409 | biostudies-literature
Project description:Brain aging causes a progressive decline in functional capacity and is a strong risk factor for dementias such as Alzheimer’s disease. To characterize age-related proteomic changes in the brain, we used quantitative proteomics to examine brain tissues, cortex and hippocampus, of mice at three age points (3, 15, and 24 months old), and quantified more than 7,000 proteins in total with high reproducibility. We found that many of the proteins upregulated with age were extracellular proteins, such as extracellular matrix proteins and secreted proteins, associated with glial cells. On the other hand, many of the significantly downregulated proteins were associated with synapses, particularly postsynaptic density, specifically in the cortex but not in the hippocampus. Our datasets will be helpful as resources for understanding the molecular basis of brain aging.
2023-10-20 | PXD041485 | JPOST Repository
Project description:Mouse macrophages J774A.1 were pre-treated with the anti-inflammatory lipid eicosapenaenoic acid (EPA) or the pro-inflammatory lipid ceramide (Cer) for 3h. Macrophages were then infected with Mycobacterium smegmatis for 1h, and total RNA was collected. In a parallel experiment, infected macrophages were infected for 1h, 4h and 24h. At these time points, macrophages were lysed, bacteria was collected and quantified by the Colony Forming Units (CFU) Assay. This provided the kinetics of the killing of Mycobacteria inside mouse macrophages. CFU experiments revealed that cells pre-treated with EPA showed an increased number of bacteria inside macrophages, in contrast to cells pre-treated with Cer. To dissect the molecular mechanisms involved in the survival and killing of mycobacteria infected macrophages, mediated by lipids, gene expression studies were performed. Cultures of Mycobacterium smegmatis mc2155 harbouring a p19-(long lived) EGFP plasmid were grown to exponential growth phase. Bacteria were pelleted, washed in PBS and resuspended in medium DMEM with a multiplicity of infection (MOI) of 10 (10 bacteria per macrophage). Clumps of bacteria were removed by ultrasonic treatment of bacterial suspensions in an ultrasonic water bath for 15 minutes, followed by a low speed centrifugation for 2 minutes. Mouse macrophages J774A.1 were pre-.treated with the anti-inflammatory lipid eicosapenaenoic acid (EPA) or the pro-inflammatory lipid ceramide (Cer), 3h before infection. Mouse macrophages J774A.1 were infected with Mycobacterium smegmatis mc2155 for 1h, at 37M-BM-:C and 5% CO2. After 1h of infection, cells were washed with PBS. After washing, 1 ml Trizol was added per well, to collect total RNA. The experimental condition were: samples 1.1, 1.2, 1.3: Untreated macrophages; samples 2.1, 2.2, 2.3: Mock treated macrophages (ethanol 1ul/ml); samples 3.1, 3.2, 3.3: EPA (15uM) treated macrophages (ethanol 1ul/ml); samples 4.1, 4.2, 4.3: Cer (5ug/ml) treated macrophages (ethanol 1ul/ml); samples 5.1, 5.2, 5.3: Untreated macrophages, infected with Mycobacterium smegmatis mc2155 for 1h; samples 6.1, 6.2, 6.3: Mock treated macrophages (ethanol 1ul/ml) infected with Mycobacterium smegmatis mc2155 for 1h; samples 7.1, 7.2, 7.3: EPA (15uM) treated macrophages (ethanol 1ul/ml) infected with Mycobacterium smegmatis mc2155 for 1h; samples 8.1, 8.2, 8.3: Cer (5ug/ml) treated macrophages (ethanol 1ul/ml) infected with Mycobacterium smegmatis mc2155 for 1h; In a parallel experiment, infected macrophages remained with the bacteria for 1h, 4h and 24h after infection. After these time points, the macrophages were lysed, the bacteria was collected and quantified by the Colony Forming Units (CFU) Assay. This provided the kinetics of the killing of non-pathogenic intracellular bacteria inside mouse macrophages. For the CFU assay, after 1h of infection, cells were washed with PBS and Gentamicin (10ug/ml) in DMEM to kill the extracellular bacteria. At discrete time points, cells were washed with PBS and lysed with sterilized water. Quantitative cultures of bacteria were performed in a 10-fold serial dilutions, inoculated on 7H10 agar plates. 5ul were plated in triplicate and the number of colonies were counted after 48h.
2015-01-20 | E-GEOD-27277 | biostudies-arrayexpress
Project description:Late onset Alzheimer’s disease (LOAD) is a progressive neurodegenerative disease with four well-established risk factors: age, APOE4 genotype, female chromosomal sex, and maternal history of AD. Each risk factor impacts multiple systems, making LOAD a complex systems biology challenge. To investigate interactions between LOAD risk factors, we performed multiple scale analyses, including metabolomics, transcriptomics, brain magnetic resonance imaging (MRI), and beta-amyloid assessment, in 16 months old male and female mice with humanized human APOE3 (hAPOE3) or APOE4 (hAPOE4) genes. Metabolomic analyses indicated a sex difference in plasma profile whereas APOE genotype determined brain metabolic profile. Consistent with the brain metabolome, gene and pathway-based RNA-Seq analyses of the hippocampus indicated increased expression of fatty acid/lipid metabolism related genes and pathways in both hAPOE4 males and females. Further, female transcription of fatty acid and amino acids pathways were significantly different from males. MRI based imaging analyses indicated that in multiple white matter tracts, hAPOE4 males and females exhibited lower fractional anisotropy than their hAPOE3 counterparts, suggesting a lower level of white matter integrity in hAPOE4 mice. Consistent with the brain metabolomic and transcriptomic profile of hAPOE4 carriers, beta-amyloid generation was detectable in 16-month-old male and female brains. These data provide therapeutic targets based on chromosomal sex and APOE genotype. Collectively, these data provide a framework for developing precision medicine interventions during the prodromal phase of LOAD, when the potential to reverse, prevent and delay LOAD progression is greatest.
2019-12-31 | GSE140205 | GEO