Abstract
BackgroundInsulin dysregulation (ID) is a key risk factor for equine endocrinopathic laminitis, but in many cases ID can only be assessed accurately using dynamic tests. The identification of other biomarkers could provide an alternative or adjunct diagnostic method, to allow early intervention before laminitis develops. The present study characterised the metabolome of ponies with varying degrees of ID using basal and postprandial plasma samples obtained during a previous study, which examined the predictive power of blood insulin levels for the development of laminitis, in ponies fed a high-sugar diet. Samples from 10 pre-laminitic (PL – subsequently developed laminitis) and 10 non-laminitic (NL – did not develop laminitis) ponies were used in a targeted metabolomic assay. Differential concentration and pathway analysis were performed using linear models and global tests.ResultsSignificant changes in the concentration of six glycerophospholipids (adj. P ≤ 0.024) and a global enrichment of the glucose-alanine cycle (adj. P = 0.048) were found to characterise the response of PL ponies to the high-sugar diet. In contrast, the metabolites showed no significant association with the presence or absence of pituitary pars intermedia dysfunction in all ponies.ConclusionsThe present results suggest that ID and laminitis risk are associated with alterations in the glycerophospholipid and glucose metabolism, which may help understand and explain some molecular processes causing or resulting from these conditions. The prognostic value of the identified biomarkers for laminitis remains to be investigated in further metabolomic trials in horses and ponies.
Highlights
Insulin dysregulation (ID) is a key risk factor for equine endocrinopathic laminitis, but in many cases ID can only be assessed accurately using dynamic tests
The model corroborated the positive correlation between serum insulin concentrations and laminitis risk [10], and so several samples from that study were selected for further investigation using the metabolomics approach
principal component analysis (PCA) analysis revealed an obvious difference between the groups both before and after feeding, the number of basal samples was small, and the laminitis groups could not be differentiated on the basis of individual metabolites, or pathways, using the basal samples alone
Summary
Insulin dysregulation (ID) is a key risk factor for equine endocrinopathic laminitis, but in many cases ID can only be assessed accurately using dynamic tests. A relatively new approach to understanding complex disease processes is metabolomics [4] This involves the Delarocque et al BMC Veterinary Research (2021) 17:56 comprehensive analysis of disparate small molecules involved in cellular processes, and has already been used, for example, to identify metabolic pathways involved in disorders such as human metabolic syndrome or risk factors for the progression towards clinical diseases such as type 2 diabetes [5]. Meier et al [10] described a method to induce laminitis in insulin-dysregulated ponies using a ‘challenge diet’ containing a high level of sugar and other non-structural carbohydrates (NSC). This method offers the advantage of exacerbating a pre-existing metabolic condition, using a natural dietary stimulus that resembles conditions that may be encountered in the field. The model corroborated the positive correlation between serum insulin concentrations and laminitis risk [10], and so several samples from that study were selected for further investigation using the metabolomics approach
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