Markers of Hepatic Insulin Clearance and Their Association With Steatosis in Hyperinsulinaemic Horses.
Abstract: Hyperinsulinaemia (HI) is an important feature of Equine Metabolic Syndrome (EMS). It has been suggested that reduced hepatic clearance of insulin contributes to HI, particularly in humans affected by metabolic dysfunction-associated steatotic liver disease (MASLD). Objective: In obese horses with HI, insulin clearance is impaired and associated with MASLD. Methods: Tissue samples were collected at post-mortem from clinically well-characterized horses with HI (n = 13; basal insulin > 20 mIU/l) and without HI (control; n = 20). Methods: Retrospective observational study. Molecular drivers of hepatic clearance (CAECAM-1, an insulin chaperone protein and IDE-Insulin Degrading Enzyme) were quantified by RT-qPCR and activity, respectively, in liver tissue. Fixed liver sections stained with hematoxylin and eosin (H&E) were assigned a histological score by two blinded observers using an equine liver disease score and a human MASLD score. Triglyceride (TG) content in liver sections, serum liver enzymes, ACTH, basal insulin, and serum triglycerides were also measured. Results: IDE activity was 2.73 (IQR 4.00 activity/mg of protein) in HI horses and 2.18 (IQR 0.55) in controls (p = 0.07). IDE activity correlated negatively with insulin (rho = 0.561, p = 0.04) but not with liver or serum TG. CEACAM-1 gene expression was higher in the HI group (2.09 ± 1.79 folds) than in controls (0.69 ± 0.62, p = 0.03). Liver disease and MASLD scores were no different between groups, whereas triglyceride liver content was higher in horses with HI (504.83 IQR 217.51 nmol/g) compared to controls (363.58 IQR 67.32 nmol/g, p = 0.04). Conclusions: MASLD is not consistently present in HI horses, but CAECAM-1 expression is higher.
© 2025 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2025-06-06 PubMed ID: 40476757PubMed Central: PMC12143019DOI: 10.1111/jvim.70143Google Scholar: Lookup
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Summary
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The research paper investigates how hyperinsulinaemia (abnormally high levels of insulin in the blood) is related to liver disease in obese horses. The study utilized post-mortem tissue samples from horses with and without hyperinsulinaemia to understand how the liver does not properly clear insulin in these cases, potentially contributing to metabolic disease and steatosis (fat accumulation in the liver).
Methodology
The researchers used a combination of techniques and measurements to assess the state of the horses’ health and metabolism:
- Tissue samples were taken from 13 horses with hyperinsulinaemia and 20 control horses (those without hyperinsulinaemia) post-mortem. Hyperinsulinaemia was defined as a basal insulin level greater than 20 mIU/l.
- They measured the activity of the Insulin Degrading Enzyme (IDE) and quantity of CEACAM-1, an insulin chaperone protein, believed to be key markers of hepatic insulin clearance.
- Two blinded observers scored fixed liver sections stained with hematoxylin and eosin using an equine liver disease score and a human steatotic liver disease score (MASLD).
- They evaluated the triglyceride (a type of fat) content in liver sections and in the horses’ serum (blood without clotting factors).
- Serum liver enzymes and ACTH (a hormone that controls the body’s response to stress) levels were also noted.
Results
The study revealed key correlations and differences between horses with hyperinsulinaemia and the control group:
- IDE activity was slightly higher in horses with hyperinsulinaemia, although this difference wasn’t statistically significant (p=0.07).
- IDE activity negatively correlated with insulin levels.
- CEACAM-1 gene expression was significantly higher in the HI group compared to the controls, indicating a difference in insulin metabolism.
- While both groups of horses had similar liver disease and MASLD scores, the hyperinsulinaemia group had a higher triglyceride content in their livers, indicating more fat accumulation.
Conclusions
Contrary to their expectations, the researchers did not find an association between hyperinsulinaemia in horses and the presence of metabolic dysfunction-associated steatotic liver disease (MASLD). This suggests that the relationship between high levels of insulin and abnormal fat accumulation and metabolism in the liver needs further study in equine models. However, they found higher CEACAM-1 expression in horses with hyperinsulinaemia, indicating a potential molecular link between insulin resistance and fat metabolism in the liver.
Cite This Article
APA
Dosi M, Scott L, Payne H, Poldy J, Keen J, McGorum B, Malbon A, Morgan R.
(2025).
Markers of Hepatic Insulin Clearance and Their Association With Steatosis in Hyperinsulinaemic Horses.
J Vet Intern Med, 39(4), e70143.
https://doi.org/10.1111/jvim.70143 Publication
Researcher Affiliations
- Scotland Rural College, Edinburgh, UK.
- Scotland Rural College, Edinburgh, UK.
- Scotland Rural College, Edinburgh, UK.
- Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Roslin, UK.
- Scotland Rural College, Edinburgh, UK.
- Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Roslin, UK.
- Scotland Rural College, Edinburgh, UK.
- Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Roslin, UK.
- Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Roslin, UK.
- Scotland Rural College, Edinburgh, UK.
- Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Roslin, UK.
MeSH Terms
- Animals
- Horses
- Horse Diseases / metabolism
- Hyperinsulinism / veterinary
- Hyperinsulinism / metabolism
- Insulin / metabolism
- Retrospective Studies
- Liver / metabolism
- Male
- Fatty Liver / veterinary
- Fatty Liver / metabolism
- Female
- Biomarkers / metabolism
- Insulysin / metabolism
- Triglycerides / blood
Conflict of Interest Statement
The authors declare no conflicts of interest.
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Citations
This article has been cited 1 times.- Aboelmaaty AM, Ahdy AM, El-Khodery S, Elgioushy M. Investigations on metabolic diseases of horses in Egypt. Front Vet Sci 2025;12:1591090.
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