Equine insulin dysregulation causes tissue specific alterations of proinflammatory cytokines and acute phase proteins in a NF-kB independent manner.

The research studied how equine metabolic syndrome (EMS), a condition analogous to human diabetes, affects the horses’ expression of certain inflammatory proteins in different tissues. This study found that insulin dysregulation in EMS increases expression of inflammatory proteins in adipose tissue, but not in skeletal muscles, independent of a specific signaling pathway, NFкB. This could provide novel possibilities for therapeutic treatments and identifying markers for EMS.

Expanding Details of the Research

• The first step of the research focused on identifying the horse groups. Two groups of five horses each were categorised as insulin-resistant (IR) or insulin-sensitive (IS), through a frequently sampled intra-venous glucose tolerance test.
• Studying the differences between these groups was done by collecting biopsies from skeletal muscle, and visceral and subcutaneous adipose tissues from both groups.
• The focus was on specific proteins: HSP90, α 2 macroglobulin (A2M), Fibrinogen α, β, γ isoforms, and cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6). The protein expression of these elements in muscle and adipose tissues was quantified via Western blotting, a common lab method used to detect specific proteins in a tissue.

Finding and Conclusion

• HSP90, A2M and IL1-β protein expressions were found to be significantly greater in visceral adipose tissue of IR horses compared to IS horses, indicating that insulin dysregulation does cause increased expression of these inflammatory proteins in a tissue-specific manner.
• Fibrinogen (α and γ) expressions were significantly increased in subcutaneous adipose tissue in IR group compared to IS group, further corroborating the point.
• In contrast to this, skeletal muscle tissue in IR horses did not show any significant difference in protein expression when compared to IS horses.
• Another significant finding was the lack of difference in the relative protein expression of total and phospho-NFκB protein expression between the adipose tissues of IR and IS horses. This means the increase in proinflammatory cytokines and acute phase proteins is independent of NFкB signaling pathway, often associated with inflammation.
• To sum up, the study found that proinflammatory cytokines and acute phase proteins were upregulated in adipose tissue, but not in the skeletal muscle due to insulin dysregulation in a horse model. These results could help to identify potential therapeutic targets or novel biomarkers for EMS condition in horses.