Circulating microRNAs in insulin resistant horses and ponies

Hugo Felipe Da Costa Santos,Tanja Maria Hess,Jason Brummer,Rebecca Splan,Brigett Mcintosh,Peter Graham

doi:10.29374/2527-2179.bjvm003620

Abstract

Insulin resistance is a prevalent disorder among horses and is associated with abnormal adiposity, laminitis, equine metabolic syndrome, and pituitary pars intermedia dysfunction. The processes leading to equine insulin resistance and associated conditions remain subject for study. MicroRNAs (miRNAs) are involved in regulation of many biological processes and diseases. The current study aimed to investigate the circulating miRNA profile of insulin resistant horses and ponies. It was hypothesized that insulin resistant horses would have a different circulating miRNA profile compared to healthy ones. 12 Thoroughbred/ Thoroughbred-cross and 12 Welsh/Dartmoor non-pregnant mares were evaluated for insulin sensitivity using frequent sampling intravenous glucose tolerance test (FSIGTT). Serum samples were collected for miRNA profiling through RT-qPCR analysis. Horses and ponies were divided into insulin sensitive (IS) or insulin resistant (IR) groups and their miRNA profiles compared. Results demonstrated that 13 miRNAs were differently expressed between IR and IS horses, 15 between IR and IS ponies, 17 between horses and ponies, and 10 between IR and IS animals (horses and ponies combined) (p<0.05). Finally, 8 miRNAs were proposed as potential regulators of equine insulin resistance. miRNA profiling is a potential tool to evaluate insulin resistance and associated conditions.

Highlights

Insulin is a hormone secreted by pancreatic beta-cells that regulates energy homeostasis in various organs, muscle, adipose tissue, and liver (Vick et al, 2007; Nirmalan & Nirmalan, 2017)
We propose that changes in miRNA profiles in equine serum lead to altered gene expression, impacting in metabolic dysfunctions, such as insulin resistance
Our preliminary study found 6 circulating miRNAs that were expressed only in insulin sensitive mares, 5 miRNAs that were found in lower quantity in insulin resistant mares, and 3 miRNAs that were found in higher quantity in insulin resistant mares, totaling 14 miRNAs differently expressed between groups in horses

Summary

Introduction

Insulin is a hormone secreted by pancreatic beta-cells that regulates energy homeostasis in various organs, muscle, adipose tissue, and liver (Vick et al, 2007; Nirmalan & Nirmalan, 2017). Insulin resistance has been associated with obesity and regional adiposity, chronic low-grade systemic inflammation, equine metabolic syndrome, pituitary pars intermedia dysfunction, and endocrinopathic laminitis (Frank et al, 2010). It has been suggested that circulating miRNAs serve as long-distance communicators between tissues (Mao et al, 2013), and they have great potential as efficient tools in studying disease-related conditions such as type 2 diabetes and metabolic syndrome in humans and laboratory animals (Ortega et al, 2014; Cui et al, 2018)

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