Potential biomarkers for laminitis-prone ponies described in study

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Insulin problems and laminitis risk are associated with alterations in the glycerophospholipid and glucose metabolism in ponies, researchers have found.
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Insulin problems and laminitis risk are associated with alterations in the glycerophospholipid and glucose metabolism in ponies, researchers have found.

Glycerophospholipids are fatty acid diglycerides that serve as a structural component of biological membranes.

Insulin dysregulation is an endocrine disorder of horses and ponies, characterized by high levels of insulin in the bloodstream. If prolonged, it can result in endocrinopathic laminitis, also known as insulin-associated laminitis.

While it is known that animals affected by insulin dysregulation may also suffer from equine metabolic syndrome and/or pituitary pars intermedia dysfunction (equine Cushing’s disease), the development of the condition and the disordered physiological processes involved have yet to be fully explained.

Julien Delarocque and his fellow researchers, writing in the journal BMC Veterinary Research, set out to characterise the metabolome of ponies with varying degrees of insulin dysregulation using base-level and after-meal plasma samples obtained during a previous study that 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 ponies (which subsequently developed laminitis) and 10 non-laminitic ponies (which did not develop laminitis) were used for targeted testing.

The researchers found that significant changes in the concentration of six glycerophospholipids and a global enrichment of the glucose-alanine cycle characterised the response of the laminitis-prone 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 any of the ponies.

The researchers noted that previous metabolomic studies around equine metabolic syndrome and insulin dysregulation in ponies and horses have described the response to oral glucose tests depending upon insulinemia, obesity, and history of laminitis.

To the authors’ knowledge, however, their work is the first to study the metabolome in relation to the future development of laminitis during a realistic dietary challenge.

They said the six glycerophospholipids characterising the post-meal metabolome of laminitis-prone ponies could serve as potential biomarkers for future risk of laminitis.

Additionally, differences in the metabolic impact of insulin suggested that laminitis-prone ponies have an insulin-sensitive liver-related metabolism, but insulin-resistant peripheral metabolism, which warrants further investigation on the proteomic level.

The authors said the costs of such analyses meant it was not possible to evaluate the predictive capabilities of these biomarkers on additional samples.

They said a genetic impact on the results cannot be excluded since only ponies were included in the present study.

“Further metabolomic investigations involving healthy, pre-laminitic and laminitic horses are warranted to clearly elucidate the prognostic value of these markers for laminitis in ponies with insulin dysregulation.”

The study team comprised Delarocque, Tobias Warnken and Karsten Feige, with the University of Veterinary Medicine Hannover, Foundation, in Germany; Dania Reiche, with Boehringer Ingelheim Vetmedica GmbH in Germany; and Alexandra Meier and Martin Sillence, with the Queensland University of Technology in Australia.

All ponies used in the study were purchased from local owners and dealers. At the end of the trial, the ponies were offered for adoption and successfully rehomed.

The project was funded by Boehringer Ingelheim Vetmedica GmbH.

Delarocque, J., Reiche, D.B., Meier, A.D. et al. Metabolic profile distinguishes laminitis-susceptible and -resistant ponies before and after feeding a high sugar diet. BMC Vet Res 17, 56 (2021). https://doi.org/10.1186/s12917-021-02763-7

The study, published under a Creative Commons License, can be read here

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