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RVC PhD Studentship - Equine metabolic syndrome associated laminitis: The role of adiponectin

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  • Full or part time
    Dr N Menzies-Gow
    Prof J Elliott
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

The overall aim of the project is to further elucidate the role of the adipose-tissue derived mediator adiponectin in equine metabolic syndrome associated laminitis.

Equine Metabolic Syndrome (EMS) is a collection of risk factors for endocrinopathic laminitis. The key feature of EMS is insulin dysregulation, which manifests as hyperinsulinaemia and/or an excessive insulin response to oral carbohydrate and/or tissue insulin resistance. Additional features include obesity, hypertriglyceridaemia and adipose dysregulation manifesting as abnormal plasma adipokine concentrations including hypoadiponectinaemia. It is well established that hyperinsulinemia can induce laminitis, but the underlying mechanism remains unclear. Current research has focused on inappropriate stimulation of insulin-like growth factor-1 (IGF-1) receptors by insulin.

Adiponectin is an adipokine with anti-inflammatory and insulin-sensitising actions and we have demonstrated that hypoadiponectinaemia, as well as hyperinsulinaemia, is a risk factor for endocrinopathic laminitis. In other species, the adiponectin and insulin signaling pathways converge at the adaptor protein APPL1 and there is emerging evidence of crosstalk between adiponectin via its receptors and both the insulin and IGF-1 receptors, resulting in increased and decreased signaling respectively.

This project will first determine whether adiponectin receptors are present in equine lamellar tissue and if there is similar crosstalk between these three signaling pathways. Secondly, the effect of hyperinsulinaemia, induction of tissue insulin resistance and pasture-induced weight gain on circulating adiponectin concentrations will be investigated in vivo. Finally, in human metabolic syndrome, dietary manipulation and pharmacologic agents are used to increase circulating adiponectin concentrations and in turn reduce the associated cardiovascular disease risk.

This project will determine whether similar approaches can be used in EMS. The effect of weight loss with or without dietary supplementation on circulating adiponectin concentrations will be evaluated. Potential pharmacologic agents will be screened in vitro through evaluation of their effects on adipocyte adiponectin production. Once identified, future studies would be required to determine whether specific agents increase circulating adiponectin concentrations in EMS horses and whether either intervention decreases the risk of endocrinopathic laminitis.

This project will allow the student to gain significant experience in a wide range of laboratory based qualitative research techniques as well as undertake in vivo studies using ponies.

Essential Requirements:
- You do not need to be a vet
- Experience of undertaking a research project

Desirable Requirements:
A vet, ideally with previous equine experience
- Previous horse handling experience
- Previous experience of undertaking a laboratory based research project
- Experience of some of the quantitative research methods to be used in the project.

This project will include both in vitro and in vivo work. The in vitro work will involve collection of tissues from horses euthanased at an abattoir for non-research purposes. The in vivo work will involve studies performed under a Home Office project license in adult ponies.

Funding Notes

This is a 3 year fully-funded studentship and is open to Home/EU applicants. International students are welcome to apply but must be able to fund the difference between UK/EU and international tuition fees.

The studentship will commence February 2020.

If you are interested in applying for this position, please follow the link below. Please use your personal statement to demonstrate any previous skills or experience you have in using quantitative research methods and horse handling.

References

1. Menzies-Gow NJ, Harris PA, Elliott J. Prospective cohort study evaluating risk factors for the development of pasture associated laminitis in the United Kingdom. Equine Vet J 2017;49:300-306.
2. Cheng KK, Lam KS, Wang B, et al. Signaling mechanisms underlying the insulin-sensitizing effects of adiponectin. Best Pract Res Clin Endocrinol Metab 2014;28:3-13.
3. Mauro L, Naimo GD, Ricchio E, et al. Cross-Talk between Adiponectin and IGF-IR in Breast Cancer. Front Oncol 2015;5:157.



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