[Show abstract][Hide abstract] ABSTRACT: Human activities are fundamentally altering the chemistry of the world's oceans. Ocean acidification (OA) is occurring against a background of warming and an increasing occurrence of disease outbreaks, posing a significant threat to marine organisms, communities and ecosystems. In the current study 1H NMR spectroscopy was used to investigate the response of the blue mussel, Mytilus edulis, to a 90 day exposure to reduced seawater pH and increased temperature, followed by a subsequent pathogenic challenge. Analysis of the metabolome revealed significant differences between male and female organisms. Furthermore, males and females are shown to respond differently to environmental stress. Whilst males were significantly affected by reduced seawater pH, increased temperature and a bacterial challenge, it was only a reduction in seawater pH that impacted females. Despite impacting males and females differently, stressors seem to act via a generalised stress response impacting both energy metabolism and osmotic balance in both sexes. This study therefore has important implications for the interpretation of metabolomic data in mussels, as well as the impact of environmental stress in marine invertebrates in general.
[Show abstract][Hide abstract] ABSTRACT: Objective. Inflammatory arthritis is associated with systemic manifestations including alterations in metabolism. We used nuclear magnetic resonance (NMR) spectroscopy–based metabolomics to assess metabolic fingerprints in serum from patients with established rheumatoid arthritis (RA) and those with early arthritis.
Methods. Serum samples were collected from newly presenting patients with established RA who were naive for disease-modifying antirheumatic drugs, matched healthy controls, and 2 groups of patients with synovitis of ≤3 months' duration whose outcomes were determined at clinical followup. Serum metabolomic profiles were assessed using 1-dimensional 1H-NMR spectroscopy. Discriminating metabolites were identified, and the relationships between metabolomic profiles and clinical variables including outcomes were examined.
Results. The serum metabolic fingerprint in established RA was clearly distinct from that of healthy controls. In early arthritis, we were able to stratify the patients according to the level of current inflammation, with C-reactive protein correlating with metabolic differences in 2 separate groups (P < 0.001). Lactate and lipids were important discriminators of inflammatory burden in both early arthritis patient groups. The sensitivities and specificities of models to predict the development of either RA or persistent arthritis in patients with early arthritis were low.
Conclusion. The metabolic fingerprint reflects inflammatory disease activity in patients with synovitis, demonstrating that underlying inflammatory processes drive significant changes in metabolism that can be measured in the peripheral blood. The identification of metabolic alterations may provide insights into disease mechanisms operating in patients with inflammatory arthritis.
[Show abstract][Hide abstract] ABSTRACT: In a search for biomarkers of health in whale sharks and as exploration of metabolomics as a modern tool for understanding animal physiology, the metabolite composition of serum in six whale sharks (Rhincodon typus) from an aquarium collection was explored using (1)H nuclear magnetic resonance (NMR) spectroscopy and direct analysis in real time (DART) mass spectrometry (MS). Principal components analysis (PCA) of spectral data showed that individual animals could be resolved based on the metabolite composition of their serum and that two unhealthy individuals could be discriminated from the remaining healthy animals. The major difference between healthy and unhealthy individuals was the concentration of homarine, here reported for the first time in an elasmobranch, which was present at substantially lower concentrations in unhealthy whale sharks, suggesting that this metabolite may be a useful biomarker of health status in this species. The function(s) of homarine in sharks remain uncertain but it likely plays a significant role as an osmolyte. The presence of trimethylamine oxide (TMAO), another well-known protective osmolyte of elasmobranchs, at 0.1-0.3 mol L(-1) was also confirmed using both NMR and MS. Twenty-three additional potential biomarkers were identified based on significant differences in the frequency of their occurrence between samples from healthy and unhealthy animals, as detected by DART MS. Overall, NMR and MS provided complementary data that showed that metabolomics is a useful approach for biomarker prospecting in poorly studied species like elasmobranchs.
PLoS ONE 11/2012; 7(11):e49379. DOI:10.1371/journal.pone.0049379 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The citric acid cycle (CAC) metabolite fumarate has been proposed to be cardioprotective; however, its mechanisms of action remain to be determined. To augment cardiac fumarate levels and to assess fumarate's cardioprotective properties, we generated fumarate hydratase (Fh1) cardiac knockout (KO) mice. These fumarate-replete hearts were robustly protected from ischemia-reperfusion injury (I/R). To compensate for the loss of Fh1 activity, KO hearts maintain ATP levels in part by channeling amino acids into the CAC. In addition, by stabilizing the transcriptional regulator Nrf2, Fh1 KO hearts upregulate protective antioxidant response element genes. Supporting the importance of the latter mechanism, clinically relevant doses of dimethylfumarate upregulated Nrf2 and its target genes, hence protecting control hearts, but failed to similarly protect Nrf2-KO hearts in an in vivo model of myocardial infarction. We propose that clinically established fumarate derivatives activate the Nrf2 pathway and are readily testable cytoprotective agents.
[Show abstract][Hide abstract] ABSTRACT: Public databases of NMR spectra of low molecular weight metabolites must be constructed to remove the major bottleneck of
metabolite identification and quantification in the analysis of metabolomics data. Two-dimensional (2-D) 1H J-resolved spectroscopy represents a popular alternative to 1-D NMR methods, resolving the highly overlapped signals characteristic
of complex metabolite mixtures across two frequency dimensions. Here we report the design, measurement and curation of, primarily,
a database of 2-D J-resolved NMR spectra. Metabolites were selected based upon their importance within metabolic pathways and their detection
potential by NMR, and prepared for analysis at pH 6.6, 7.0 and 7.4. Sixteen NMR spectra were recorded for each metabolite
using a 500MHz spectrometer, including 1-D and 2-D J-resolved spectra, different water suppression methods and different acquisition parameters. Some metabolites were removed
due to limited solubility, poor NMR signal quality or contamination, and the final dataset comprised of 3328 NMR spectra arising
from 208 metabolite standards. These data are housed in a purpose-built MySQL database (Birmingham Metabolite Library; BML-NMR)
containing over 100 separate tables and allowing the efficient storage of raw free-induction-decays (FIDs), 1-D and 2-D NMR
spectra and associated metadata. The database is compliant with the Metabolomics Standards Initiative (MSI) endorsed reporting
requirements, with some necessary amendments. Library data can be accessed freely and searched through a custom written web
interface (www.bml-nmr.org). FIDs, NMR spectra and associated metadata can be downloaded according to a newly implemented MSI-compatible XML schema.
KeywordsMetabolite database–Metabolomics database–Metabolic pathway–Downloadable