Novel Mechanisms Point to New Diagnostic Target for EMS

Obesity contributes to insulin dysregulation (ID) and is a central feature of equine metabolic syndrome (EMS). Horses with ID have high circulating levels of insulin, which can lead to the development of laminitis. The underlying mechanisms by which obesity contributes to ID in horses, however, remain unclear.

Clarifying the exact mechanisms involved in the development of ID plays an important role in better understanding the disease and potentially limiting hyperinsulinemia-associated laminitis. In addition, an improved understanding of obesity and ID will help identify biomarkers of disease for diagnostic purposes and potential targets for future therapeutic agents.

Extrapolating data from human diabetes, a condition like EMS, Oklahoma State University researchers suggested that inflammation and the production of inflammatory mediators from adipose (fat) tissue may be involved.^* The team therefore measured various inflammatory mediators in adipose tissue samples collected from horses with and without IR.

The proinflammatory cytokines interleukin(IL)-1β and IL-6 were both increased in visceral adipose tissue samples collected from horses with IR. Visceral fat is located within the abdominal cavity, around the internal organs. Of particular interest was finding that the acute phase protein alpha-2-macroglobulin (A2M) was also increased in visceral adipose tissue samples in IR horses. Neither of those interleukins nor A2M was elevated in subcutaneous fat samples in IR horses.

According to the researchers, these results suggested that IR leads to a cytokine-mediated increase in acute phase proteins, like A2M, produced by the liver in the face of an inflammatory event. This low-grade, chronic inflammation of adipose tissue may further exacerbate IR.

“The researchers also suggested that A2M and other inflammatory cytokines could represent novel biomarkers for the early detection of IR and lead to potential therapeutic options for horses diagnosed with EMS,” explained Katie Young, Ph.D., a Kentucky Equine Research nutritionist.

“For horses at risk of ID or EMS, dietary and management options often focus on maintaining appropriate body condition and participating in regular exercise. Weight management and exercise increase insulin sensitivity in horses and may help reduce the risk of IR and laminitis in those prone to EMS,” said Young.

For overweight or obese horses or even easy keepers, dietary management strategies such as offering forage-based diets supplemented with a ration balancer may provide all the necessary nutrients without excess calories.

“Look for low-intake vitamin/mineral supplements,” Young recommended.

^*Jayathilake, W.M.N.K., M. Furr, C. Risco, and V.A. Lacombe. 2022. Equine insulin dysregulation causes tissue specific alterations of proinflammatory cytokines and acute phase proteins in a NF-kB independent manner. Veterinary Immunology and Immunopathology 253:110500.