Detection of endoplasmic reticulum stress and the unfolded protein response in naturally-occurring endocrinopathic equine laminitis.
Authors: Cassimeris Lynne, Engiles Julie B, Galantino-Homer Hannah
Journal: BMC veterinary research
Summary
# Editorial Summary Endocrinopathic laminitis, commonly linked to conditions like equine metabolic syndrome and pituitary pars intermedia dysfunction that cause chronically elevated insulin levels, remains a significant welfare concern with poorly understood cellular mechanisms. Cassimeris and colleagues investigated whether the excessive anabolic signalling triggered by hyperinsulinemia in lamellar tissue initiates a cellular stress response—specifically endoplasmic reticulum (ER) stress—by examining protein markers of the unfolded protein response in laminae biopsies from naturally laminitic horses compared to healthy controls. The researchers detected increased expression of key ER stress markers in lamellar tissue from endocrinopathic laminitis cases, supporting their hypothesis that chronic over-stimulation of growth and metabolic pathways precipitates cellular dysfunction analogous to human metabolic disease. These findings suggest that the lamellar pathology in endocrinopathic laminitis arises not simply from insulin's direct effects but from a maladaptive cellular stress cascade, offering a mechanistic framework for understanding why stringent glycaemic control is crucial in managing laminitis-prone horses. For practitioners, this work reinforces the importance of aggressive insulin management in at-risk animals and hints that future therapeutic strategies might target ER stress pathways alongside traditional insulin-lowering approaches.
Read the full abstract on PubMed
Practical Takeaways
- •Horses with endocrinopathies causing hyperinsulinemia develop laminitis through cellular stress mechanisms involving protein misfolding—aggressive insulin control may help prevent tissue damage progression
- •Understanding that endocrinopathic laminitis involves cellular stress at the ER level supports the importance of metabolic management and early endocrinopathy detection in at-risk horses
- •This cellular mechanism explains why chronically hyperinsulinemic horses are vulnerable to laminitis and emphasizes need for insulin regulation through diet, exercise, and medication where appropriate
Key Findings
- •Lamellar tissue from horses with naturally-occurring endocrinopathic laminitis expresses protein markers of endoplasmic reticulum stress
- •Chronic hyperinsulinemia over-stimulates pro-growth and anabolic signaling pathways in lamellar tissue
- •Endoplasmic reticulum stress contributes to lamellar tissue pathology in endocrinopathic laminitis, similar to mechanisms in human metabolic diseases
- •The unfolded protein response is activated in lamellar tissue of laminitic horses with endocrinopathies