A liquid chromatography-tandem mass spectrometry-based investigation of the lamellar interstitial metabolome in healthy horses and during experimental laminitis induction.
Abstract: Lamellar bioenergetic failure is thought to contribute to laminitis pathogenesis but current knowledge of lamellar bioenergetic physiology is limited. Metabolomic analysis (MA) can systematically profile multiple metabolites. Applied to lamellar microdialysis samples (dialysate), lamellar bioenergetic changes during laminitis (the laminitis metabolome) can be characterised. The objectives of this study were to develop a technique for targeted MA of lamellar and skin dialysates in normal horses, and to compare the lamellar and plasma metabolomic profiles of normal horses with those from horses developing experimentally induced laminitis. Archived lamellar and skin dialysates (n = 7) and tissues (n = 6) from normal horses, and lamellar dialysate and plasma from horses given either 10 g/kg oligofructose (treatment group, OFT; n = 4) or sham (control group, CON; n = 4) were analysed. The concentrations of 44 intermediates of central carbon metabolism (CCM) were determined using liquid chromatography-tandem mass spectrometry. Data were analysed using multivariate (MVA) and univariate (UVA) analysis methods. The plasma metabolome appeared to be more variable than the lamellar metabolome by MVA, driven by malate, pyruvate, aconitate and glycolate. In lamellar dialysate, these metabolites decreased in OFT horses at the later time points. Plasma malate was markedly increased after 6 h in OFT horses. Plasma malate concentrations between OFT and CON at this time point were significantly different by UVA. MA of lamellar CCM was capable of differentiating horses developing experimental laminitis from controls. Lamellar malate, pyruvate, aconitate and glycolate, and plasma malate alone were identified as the source of differentiation between OFT and CON groups. These results highlighted clear discriminators between OFT and CON horses, suggesting that changes in energy metabolism occur locally in the lamellar tissue during laminitis development. The biological significance of these alterations requires further investigation.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication Date: 2015-08-04 PubMed ID: 26364239DOI: 10.1016/j.tvjl.2015.07.031Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Biochemistry
- Clinical Study
- Comparative Study
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Energy Metabolism
- Equine Diseases
- Equine Health
- Experimental Methods
- High-performance Liquid Chromatography (HPLC)
- Horses
- Lameness
- Metabolic Health
- Metabolites
- Metabolomics
- Pathogenesis
- Physiology
- Veterinary Medicine
- Veterinary Research
Summary
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The research is about investigating the changes in energy metabolism in horse’s lamellar tissue during the development of laminitis, a painful disease of the hoof. This was done by employing liquid chromatography-tandem mass spectrometry to determine the concentration of different compounds involved in energy metabolism.
Objective and Methodology
- The primary aim of the study was to develop a method for metabolomic analysis of lamellar and skin dialysates in healthy horses and to compare the metabolic profiles of these normal horses with those that have experimentally induced laminitis.
- The researchers utilized archived samples from healthy horses, and from horses which were given oligofructose to induce laminitis.
- The concentrations of 44 compounds involved in central carbon metabolism were measured using a technique called liquid chromatography-tandem mass spectrometry. The resulting data were then analyzed using both multivariate and univariate analysis methods.
Findings
- The results revealed that the plasma metabolome was more variable than the lamellar metabolome.
- The changes in the metabolome were primarily driven by four compounds: malate, pyruvate, aconitate, and glycolate.
- In the lamellar dialysate of horses which were given oligofructose to induce laminitis, these four compounds decreased at later time points. Plasma malate, in particular, showed a marked increase after six hours in these horses.
- The study discovered a significant difference in plasma malate concentrations at this time point between the control horses and the ones with induced laminitis.
Conclusions and Implications
- The metabolomic analysis of lamellar central carbon metabolism was able to differentiate between horses developing experimental laminitis and control horses, indicating changes in energy metabolism in the lamellar tissue during laminitis development.
- The compounds malate, pyruvate, aconitate, and glycolate in lamellar tissue, and malate alone in plasma were identified as the primary source of differentiation between the two groups.
- These findings suggest that there are discernible changes in energy metabolism locally in the lamellar tissue during laminitis development. However, the biological importance of these alterations warrants further investigation.
Cite This Article
APA
Medina-Torres CE, van Eps AW, Nielsen LK, Hodson MP.
(2015).
A liquid chromatography-tandem mass spectrometry-based investigation of the lamellar interstitial metabolome in healthy horses and during experimental laminitis induction.
Vet J, 206(2), 161-169.
https://doi.org/10.1016/j.tvjl.2015.07.031 Publication
Researcher Affiliations
- Australian Equine Laminitis Research Unit, School of Veterinary Science, Faculty of Science, The University of Queensland, Gatton Campus, Gatton, QLD 4343, Australia. Electronic address: c.medina@pferd.vetmed.uni-muenchen.de.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, Faculty of Science, The University of Queensland, Gatton Campus, Gatton, QLD 4343, Australia.
- Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
- Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia; Metabolomics Australia - Queensland Node, AIBN, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia; School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia.
MeSH Terms
- Animals
- Chromatography, Liquid
- Foot / pathology
- Foot Diseases / metabolism
- Foot Diseases / veterinary
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Inflammation / metabolism
- Inflammation / veterinary
- Skin / chemistry
- Skin / metabolism
- Tandem Mass Spectrometry
Citations
This article has been cited 5 times.- Espinosa MI, Gonzalez-Garcia RA, Valgepea K, Plan MR, Scott C, Pretorius IS, Marcellin E, Paulsen IT, Williams TC. Adaptive laboratory evolution of native methanol assimilation in Saccharomyces cerevisiae.. Nat Commun 2020 Nov 4;11(1):5564.
- Tefera TW, Bartlett K, Tran SS, Hodson MP, Borges K. Impaired Pentose Phosphate Pathway in the Spinal Cord of the hSOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis.. Mol Neurobiol 2019 Aug;56(8):5844-5855.
- Ward MS, Flemming NB, Gallo LA, Fotheringham AK, McCarthy DA, Zhuang A, Tang PH, Borg DJ, Shaw H, Harvie B, Briskey DR, Roberts LA, Plan MR, Murphy MP, Hodson MP, Forbes JM. Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes.. Sci Rep 2017 Nov 9;7(1):15190.
- Mills RJ, Titmarsh DM, Koenig X, Parker BL, Ryall JG, Quaife-Ryan GA, Voges HK, Hodson MP, Ferguson C, Drowley L, Plowright AT, Needham EJ, Wang QD, Gregorevic P, Xin M, Thomas WG, Parton RG, Nielsen LK, Launikonis BS, James DE, Elliott DA, Porrello ER, Hudson JE. Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest.. Proc Natl Acad Sci U S A 2017 Oct 3;114(40):E8372-E8381.
- McDonald TS, Carrasco-Pozo C, Hodson MP, Borges K. Alterations in Cytosolic and Mitochondrial [U-(13)C]Glucose Metabolism in a Chronic Epilepsy Mouse Model.. eNeuro 2017 Jan-Feb;4(1).
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