Gene Expression Differences of Adipose and Gluteal Muscle Tissues in Four Breeds of Horses with a Range of Insulin Sensitivities

Equine metabolic syndrome (EMS) and associated insulin dysregulation (ID) has been identified as the most common cause of laminitis. Certain breeds seem susceptible to EMS, and we have identified breed differences in metabolic phenotypes. Muscle and adipose tissue have large roles in glucose and insulin regulation. Here we compare gene expression within the tailhead adipose tissue (TAT) and gluteal muscle in different breeds. Frequently sampled intravenous glucose tolerance tests (FSIGTT), TAT, and muscle biopsies were performed in 28 geldings from four breeds. Gene expression in gluteal muscle and TAT was measured using RNASeq. Differential gene expression was determined using HTSeq and Limma Voom. Functional analysis of genes was performed using Ingenuity Pathway Analysis (IPA). Each breed had a range of insulin sensitivities based on minimal model analysis of the FSIGTT and uniquely differentially expressed genes in each tissue (7-1347 in adipose, 94-691 in muscle). In TAT, top networks in Arabians and Welsh Ponies (WP) were Carbohydrate Metabolism and Developmental Disorders/Lipid Metabolism respectively. WP had upstream analysis activation of cytochrome p450 reductase. There was upstream activation of hypoxia-inducible factor 1-alpha and transforming growth factor beta 1 in Morgans and Arabians, with deactivation in Arabians and activation in Morgans of forkhead box protein 01, C-X-C Motif Chemokine Ligand 12, and growth hormone. In muscle, the top QH network was Lipid Metabolism, with upstream analysis showing deactivation of fenofibrate, pirinixic acid, and rosiglitazone. The top WP network was Energy Production/Lipid Metabolism. Breed specific patterns of differentially expressed genes may contribute to ID.