A liquid chromatography-tandem mass spectrometry-based investigation of the lamellar interstitial metabolome in healthy horses and during experimental laminitis induction.
Authors: Medina-Torres C E, van Eps A W, Nielsen L K, Hodson M P
Journal: Veterinary journal (London, England : 1997)
Summary
# Editorial Summary Metabolomic analysis of lamellar tissue offers a novel window into the bioenergetic dysfunction thought to underpin laminitis pathogenesis, yet the specific metabolic changes occurring within the lamellae during disease development remain poorly characterised. Medina-Torres and colleagues used liquid chromatography-tandem mass spectrometry to measure 44 intermediates of central carbon metabolism in lamellar microdialysate and plasma from healthy horses and those given oligofructose (a recognised laminitis trigger), establishing the first targeted metabolomic profile of lamellar tissue during experimental laminitis induction. Key discriminators emerged between horses developing laminitis and controls: lamellar concentrations of malate, pyruvate, aconitate and glycolate decreased significantly at later timepoints in affected horses, whilst plasma malate showed a marked rise at 6 hours post-challenge and diverged significantly from sham controls at this critical window. These findings provide evidence that measurable alterations in energy metabolism occur locally within lamellar tissue during laminitis development, implicating specific disruptions to central carbon metabolism rather than systemic metabolic derangement alone. For practitioners, this research establishes a metabolomic framework for investigating laminitis pathogenesis and suggests that future diagnostic or therapeutic interventions might usefully target these identified metabolic intermediates, though the biological significance of these changes and their precise role in tissue failure require further investigation.
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Practical Takeaways
- •Lamellar bioenergetic failure is a measurable and detectable metabolic process during laminitis development, supporting the hypothesis that energy metabolism dysfunction contributes to disease pathogenesis
- •Specific metabolites (malate, pyruvate, aconitate, glycolate) could potentially serve as early biomarkers for laminitis development, though further clinical validation is needed before practical application
- •Local metabolic changes in lamellar tissue precede or occur independently of systemic plasma metabolic changes, suggesting therapeutic interventions targeting lamellar metabolism may warrant investigation
Key Findings
- •Metabolomic analysis of lamellar dialysate successfully differentiated horses developing experimental laminitis from controls using 44 central carbon metabolism intermediates
- •Lamellar malate, pyruvate, aconitate and glycolate concentrations decreased at later time points in oligofructose-treated horses, indicating local metabolic changes
- •Plasma malate concentration was markedly increased 6 hours after oligofructose administration and was significantly different between laminitis and control groups
- •The lamellar metabolome showed less variability than the plasma metabolome, suggesting local tissue-specific metabolic changes during laminitis development