The association of metabolic syndrome and iron overload, indicated by high serum ferritin concentration in humans, is well-known (Stechemesser, Eder et al. 2017). In other mammals, like captive black rhinos and its most closely related species, the horse, iron overload is primarily dietary in origin. Due to the similarity between these two species, horses were used as an alternative model by researchers studying the relationship between metabolic disease and iron overload in captive black rhinos (Nielsen, Vick et al. 2012).
Because black rhinos are critically endangered, and captive animals have diseases induced or exacerbated by iron overload, treatment and prevention is paramount to improve their health and longevity. Therefore, feeding protocols that limit dietary iron intake were utilized in captive rhinos. This resulted in the successful reduction of hyperferritinemia, an approach that should improve the health and longevity for this endangered species (Sullivan, Mylniczenko et al. 2020).
Excessive iron is stored in body tissues, spleen, liver, small intestine, and lung. In all species studied, elevated body iron storage is both a risk factor and a consequence of insulin resistance, while reducing body iron reduces risk and improves insulin sensitivity. Drs. Eleanor Kellon and Kathleen Gustafson described the association of hyperferritinemia and hyperinsulinemia (high serum ferritin and insulin) in horses (Kellon and Gustafson 2020). While emphasizing that high dietary iron is an unlikely independent causal factor in the development of equine metabolic syndrome (EMS), they stressed that the association between iron overload and EMS in horses is worthy of research, as it has been in other species. Their publication was recognized by other researchers studying human Alzheimer’s disease (AD).
Human type II diabetes (T2DM) with abnormal insulin signaling has been linked to Alzheimer’s Disease (AD). Researchers studied the brains of aged donkeys and found lesions similar to those found in humans with AD (Malbon, Lorena et al. 2022). They say, “The finding of shared neuropathological changes with humans opens the door to perhaps the most intriguing aspect; their (donkey and human) shared susceptibility to metabolic dysfunctions. The triad of T2DM, obesity, and AD are intricately linked in humans with insulin dysregulation one of the main common factors. Equids, in particular donkeys, are known to be prone to their own version of insulin resistance, in the form of equine metabolic syndrome (EMS). An additional area of interest for further investigation is the link between iron levels, metabolic syndrome, and neurodegeneration. Ferritin levels have been linked to hyperinsulinemia in horses (Kellon and Gustafson 2020), whilst in humans altered iron homeostasis is known to occur in numerous forms of neurodegeneration.”
The ECIR Group Inc. encourages and supports further research aimed at increasing knowledge of the complex association and mechanisms surrounding EMS, PPID (Pituitary Pars Intermedia Dysfunction), iron overload, and neurodegeneration (McFarlane, Dybdal et al. 2005, McFarlane 2007). This is the time for research directed towards equines with EMS and/or PPID as a primary research model, instead of a secondary stand-in for other species.
REFERENCES
Kellon, E. M. and K. M. Gustafson (2020). Possible dysmetabolic hyperferritinemia in hyperinsulinemic horses. Open Vet J 9(4): 287-293.
Malbon, A. J., S. Lorena, W. L. A., G.-M. Danielle, P. Georgios, M. Neil, S. Tobias, M. Bruce and H. Caroline (2022). Alzheimer-like pathology in the parietal cortex and hippocampus of aged donkeys. Neurobiology of Aging 113: 7-14.
McFarlane, D. (2007). Advantages and limitations of the equine disease, pituitary pars intermedia dysfunction as a model of spontaneous dopaminergic neurodegenerative disease. Ageing Research Reviews Ageing Research Reviews 6(1): 54-63.
McFarlane, D., N. Dybdal, M. T. Donaldson, L. Miller and A. E. Cribb (2005). Nitration and increased alpha-synuclein expression associated with dopaminergic neurodegeneration in equine pituitary pars intermedia dysfunction. J Neuroendocrinol 17(2): 73-80.
Nielsen, B. D., M. M. Vick and P. M. Dennis (2012). A potential link between insulin resistance and iron overload disorder in browsing rhinoceroses investigated through the use of an equine model. J Zoo Wildl Med 43(3 Suppl): S61-65.
Stechemesser, L., S. K. Eder, A. Wagner, W. Patsch, A. Feldman, M. Strasser, S. Auer, D. Niederseer, U. Huber-Schonauer, B. Paulweber, S. Zandanell, S. Ruhaltinger, D. Weghuber, E. Haschke-Becher, C. Grabmer, E. Rohde, C. Datz, T. K. Felder and E. Aigner (2017). Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism. Mol Metab 6(1): 38-47.
Sullivan, K. E., N. D. Mylniczenko, S. E. Nelson, Jr., B. Coffin and S. R. Lavin (2020). Practical Management of Iron Overload Disorder (IOD) in Black Rhinoceros (BR; Diceros bicornis). Animals (Basel) 10(11).
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About ECIR Group Inc.
Started in 1999, the ECIR Group is the largest field-trial database for PPID and EMS in the world and provides the latest research, diagnosis, and treatment information, in addition to dietary recommendations for horses with these conditions. Even universities do not and cannot compile and follow long term as many in-depth case histories of PPID/EMS horses as the ECIR Group.
In 2013 the Equine Cushing's and Insulin Resistance Group Inc., an Arizona nonprofit corporation, was approved as a 501(c)3 public charity. Tax deductible contributions and grants support ongoing research, education, and awareness of Equine Cushing's Disease/PPID and EMS.
THE MISSION of the ECIR Group Inc. is to improve the welfare of equines with metabolic disorders via a unique interface between basic research and real-life clinical experience. Prevention of laminitis is the ultimate goal. The ECIR Group serves the scientific community, practicing clinicians, and owners by focusing on investigations most likely to quickly, immediately, and significantly benefit the welfare of the horse.