Metabolomic and lipidomic profiles in response to exogenous insulin and GLP-1 infusions during prolonged fasting
Ontology highlight
ABSTRACT:
ORGANISM(S): Mirounga Angustirostris
TISSUE(S): Blood
DISEASE(S): Diabetes
PROVIDER: ST000107 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description: Not available
| ST000048 | MetabolomicsWorkbench
Project description:This application requests funding to access state-of-the-art metabolomics and lipidomic platforms at the NIH West Coast Metabolomics Center to analyze plasma samples from recent insulin and glucagon-like peptide-1 (GLP-1) infusion experiments performed in prolong-fasted elephant seals. This suite of studies was designed to better assess the mechanisms contributing to the onset of an insulin resistantlike condition induced by prolonged food deprivation/starvation in mammals. Because elephant seals have evolved robust physiological mechanisms that have allowed them to naturally tolerate such protracted bouts of fasting, they provide an ideal model to address our central hypothesis that increased lipid utilization late in the fast contributes to insulin resistance in elephant seals. Insulin resistance is a common consequence of fasting in mammals and, while the mechanisms by which it manifests are still unclear, a metabolic shift favoring increased mobilization and utilization of lipids during prolonged food deprivation may be a principal causative factor. Insulin resistance has a negative connotation due to its association with obesity and diabetes among humans, but it has been suggested to be an adaptive response to food deprivation.
2019-07-01 | MSV000084033 | GNPS
Project description:BACKGROUND: Domestic broiler chickens rapidly accumulate adipose tissue due to intensive genetic selection for rapid growth and are naturally hyperglycemic and insulin resistant, making them an attractive addition to the suite of rodent models used for studies of obesity and type 2 diabetes in humans. Furthermore, chicken adipose tissue is considered as poorly sensitive to insulin and lipolysis is under glucagon control. Excessive fat accumulation is also an economic and environmental concern for the broiler industry due to the loss of feed efficiency and excessive nitrogen wasting, as well as a negative trait for consumers who are increasingly conscious of dietary fat intake. Understanding the control of avian adipose tissue metabolism would both enhance the utility of chicken as a model organism for human obesity and insulin resistance and highlight new approaches to reduce fat deposition in commercial chickens. RESULTS: We combined transcriptomics and metabolomics to characterize the response of chicken adipose tissue to two energy manipulations, fasting and insulin deprivation in the fed state. Sixteen to 17 day-old commercial broiler chickens (ISA915) were fed ad libitum, fasted for five hours, or fed but deprived of insulin by injections of anti-insulin serum. Pair-wise contrasts of expression data identified a total of 2016 genes that were differentially expressed after correction for multiple testing, with the vast majority of differences due to fasting (1780 genes). Gene Ontology and KEGG pathway analyses indicated that a short term fast impacted expression of genes in a broad selection of pathways related to metabolism, signaling and adipogenesis. The effects of insulin neutralization largely overlapped with the response to fasting, but with more modest effects on adipose tissue metabolism. Tissue metabolomics indicated unique effects of insulin on amino acid metabolism. CONCLUSIONS: Collectively, these data provide a foundation for further study into the molecular basis for adipose expansion in commercial poultry and identify potential pathways through which fat accretion may be attenuated in the future through genetic selection or management practices. They also highlight chicken as a useful model organism in which to study the dynamic relationship between food intake, metabolism, and adipose tissue biology.
| S-EPMC3503602 | biostudies-literature
Project description:COVID-19 is a systemic infection that exerts significant impact on the metabolism. Yet, there is little information on how SARS-CoV-2 affects metabolism. Using NMR spectroscopy, we measured the metabolomic and lipidomic serum profile from 263 (training cohort) + 135 (validation cohort) symptomatic patients hospitalized after positive PCR testing for SARS-CoV-2 infection. We also established the profiles of 280 persons collected before the coronavirus pandemic started. Principal-component analysis discriminated both cohorts, highlighting the impact that the infection has on overall metabolism. The lipidomic analysis unraveled a pathogenic redistribution of the lipoprotein particle size and composition to increase the atherosclerotic risk. In turn, metabolomic analysis reveals abnormally high levels of ketone bodies (acetoacetic acid, 3-hydroxybutyric acid, and acetone) and 2-hydroxybutyric acid, a readout of hepatic glutathione synthesis and marker of oxidative stress. Our results are consistent with a model in which SARS-CoV-2 infection induces liver damage associated with dyslipidemia and oxidative stress.
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Project description:Dedifferentiated liposarcoma (DDLPS) is an aggressive mesenchymal cancer marked by amplification of MDM2, an inhibitor of the tumor suppressor TP53. DDLPS patients with higher MDM2 amplification have lower chemotherapy sensitivity and worse outcome than patients with lower MDM2 amplification. We hypothesized that MDM2 amplification levels may be associated with changes in DDLPS metabolism. Six patient-derived DDLPS cell line models were subject to comprehensive metabolomic (Metabolon) and lipidomic (SCIEX 5600 TripleTOF-MS) profiling to assess associations with MDM2 amplification and their responses to metabolic perturbations. Comparing metabolomic profiles between MDM2 higher and lower amplification cells yielded a total of 17 differentially abundant metabolites across both panels (FDR < 0.05, log2 fold change < 0.75), including ceramides, glycosylated ceramides, and sphingomyelins. Disruption of lipid metabolism through statin administration resulted in a chemo-sensitive phenotype in MDM2 lower cell lines only, suggesting that lipid metabolism may be a large contributor to the more aggressive nature of MDM2 higher DDLPS tumors. This study is the first to provide comprehensive metabolomic and lipidomic characterization of DDLPS cell lines and provides evidence for MDM2-dependent differential molecular mechanisms that are critical factors in chemoresistance and could thus affect patient outcome.
| S-EPMC7463633 | biostudies-literature
Project description:Coffee (Coffea spp.) is one of the most popular refreshing beverages globally. Coffee lipid diversity has untapped potential for improving coffee marketability because lipids contribute significantly to both the health benefits and cup quality of coffee. However, in spite of its potential importance, there have not been extensive studies of lipids among C. canephora genotypes. In this study, ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) profiling of lipid molecules was performed for 30 genotypes consisting of 15 cultivated and 15 conserved genotypes of C. canephora in Southwestern Nigeria. We identified nine classes of lipids in the 30 genotypes which belong to the 'Niaouli', 'Kouillou' and 'Java Robusta' group: among these, the most abundant lipid class was the triacylglycerols, followed by the fatty acyls group. Although 'Niaouli' diverged from the 'Kouillou' and 'Java Robusta' genotypes when their lipid profiles were compared, there was greater similarity in their lipid composition by multivariate analysis, compared to that observed when their primary metabolites and especially their secondary metabolite profiles were examined. However, distinctions could be made among genotypes. Members of the fatty acyls group had the greatest power to discriminate among genotypes, however, lipids that were low in abundance e.g. a cholesterol ester (20:3), and phosphotidylethanolamine (34:0) were also helpful to understand the relationships among C. canephora genotypes. The divergent lipid profiles identified among the C. canephora genotypes, correlated with their Single Nucleotide Polymorphism grouping as assessed by genotype-by-sequencing, and will be exploited to improve coffee cup quality.
| S-EPMC7888636 | biostudies-literature
Project description:The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.
| S-EPMC7877736 | biostudies-literature
Project description:BackgroundSepsis is defined as a dysfunctional host response to infection. The diverse clinical presentations of sepsis pose diagnostic challenges and there is a demand for enhanced diagnostic markers for sepsis as well as an understanding of the underlying pathological mechanisms involved in sepsis. From this perspective, metabolomics has emerged as a potentially valuable tool for aiding in the early identification of sepsis that could highlight key metabolic pathways and underlying pathological mechanisms.ObjectiveThe aim of this investigation is to explore the early metabolomic and lipidomic profiles in a prospective cohort where plasma samples (n = 138) were obtained during ambulance transport among patients with infection according to clinical judgement who subsequently developed sepsis, patients who developed non-septic infection, and symptomatic controls without an infection.MethodsMultiplatform metabolomics and lipidomics were performed using UHPLC-MS/MS and UHPLC-QTOFMS. Uni- and multivariable analysis were used to identify metabolite profiles in sepsis vs symptomatic control and sepsis vs non-septic infection.ResultsUnivariable analysis disclosed that out of the 457 annotated metabolites measured across three different platforms, 23 polar, 27 semipolar metabolites and 133 molecular lipids exhibited significant differences between patients who developed sepsis and symptomatic controls following correction for multiple testing. Furthermore, 84 metabolites remained significantly different between sepsis and symptomatic controls following adjustment for age, sex, and Charlson comorbidity score. Notably, no significant differences were identified in metabolites levels when comparing patients with sepsis and non-septic infection in univariable and multivariable analyses.ConclusionOverall, we found that the metabolome, including the lipidome, was decreased in patients experiencing infection and sepsis, with no significant differences between the two conditions. This finding indicates that the observed metabolic profiles are shared between both infection and sepsis, rather than being exclusive to sepsis alone.
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| S-EPMC10090499 | biostudies-literature
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| S-EPMC4223040 | biostudies-literature