Abstract

Equine metabolic syndrome (EMS) is characterized by adiposity, insulin dysregulation and increased risk for laminitis. Increased levels of specific liver enzymes in the peripheral blood are typical findings in horses diagnosed with EMS. Current management of EMS is based on caloric restriction and increased physical activity. However, new potential treatment options are arising such as the transplantation of autologous adipose stem cells (ASC). However, cytophysiological properties of ASC derived from EMS horses are impaired which strongly limits their therapeutic potential. We hypothesized, that in vitro pharmacotherapy of those cells with 5-azacytidine (AZA) and resveratrol (RES) before their clinical application can reverse the aged phenotype of those cells and improve clinical outcome of autologous therapy. A 9 year old Dutch Warmblood Horse used for driving, was presented with severe obesity, insulin resistance. After EMS diagnosis, the animal received three intravenous injections of autologous, AZA/RES treated ASCs at weekly intervals. The therapeutic effect was assessed by the analysis of liver specific enzymes in the blood. ASC-transplantation reduced levels of glutamate dehydrogenase (GLDH), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH) and aspartate transaminase (AST). This case report demonstrates the therapeutic potential of this intervention for EMS as well as apt utility of autologous, rejuvenated ASC injections.

Highlights

  • Equine metabolic syndrome (EMS) has become more and more prevalent disorder affecting horses all over the world

  • Our results revealed that EMS-adipose stem cells (ASC) are characterized by decreased proliferation rate, increased apoptosis and senescence, oxidative stress and mitochondrial impairment as well as abnormal DNA methylation [19]

  • A similar trend was observed for lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels which decreased in peripheral blood after ASC-injections. (Fig. 3b)

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Summary

Introduction

Equine metabolic syndrome (EMS) has become more and more prevalent disorder affecting horses all over the world. EMS is characterized by the compilation of following factors: (i) regional adiposity in the neck, tail head and above the eye, (ii) insulin resistance and (iii) laminitis, both chronic and/or acute [1]. Recent findings strongly supports the thesis, that liver may play a central and crucial role in the development of insulin resistance and EMS. On the one hand dietary management is currently a first choice intervention for the treatment of EMS horses. Dietary protocol for EMS horses should include a low glycaemic index and high-fibre as well as low non-structural carbohydrate (NSC) contents. Since no effective therapy for EMS exists, searching for a novel, valuable and effective strategy to increase insulin sensitivity in affected individuals is mandatory

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