Researchers exploring the genetic basis of obesity and related metabolic diseases in humans and companion animals discussed the paradoxes surrounding equine metabolic syndrome in a just-published paper.
University of Cambridge researchers Natalie Walls and Eleanor Raffan, in a review in the journal Genes, note that obesity is one of the most prevalent health conditions in humans and companion animals globally.
It is associated with premature mortality, metabolic dysfunction, and multiple health conditions across species.
“Obesity is, therefore, of importance in the fields of medicine and veterinary medicine,” the pair wrote.
The regulation of obesity is vulnerable to disruption by many genetic and environmental factors, they said.
“It is well established that the heritability of obesity is high in humans and laboratory animals, with ample evidence that the same is true in companion animals.”
Dealing with horses, Walls and Raffan noted that, as in other companion animal species, equine obesity is common. An estimated 20% to 70% of horses are overweight/obese.
“This is a significant clinical problem because obesity is a risk factor for the development of laminitis, a common, crippling disorder of the equine hoof.
“That association is thought to be mediated predominantly via a collection of risk factors known as equine metabolic syndrome (EMS).”
EMS was first described in 2002 and the links between obesity and laminitis have been extensively studied since, although it is acknowledged that the current working understanding requires refinement.
“EMS is defined by the presence of insulin dysregulation, characterised by clinical features including hyperinsulinaemia (either at baseline or in response to glucose challenge), hyperglycaemia, and/or evidence of peripheral insulin resistance.
“Insulin resistance is commonly present in EMS, although there has been some debate as to whether that is always true and if alternative routes by which insulin dysregulation may develop/exist. Notably, although obesity and EMS are common, it is rare for horses and ponies to become diabetic.
“Not all overweight equines develop EMS, nor does EMS always cause laminitis. Similarly, not all horses that have clinical features of EMS are overweight.
“Those paradoxes exist between individuals and across breeds, with some breeds apparently particularly prone to developing laminitis despite only moderate weight gain.”
This, they say, is reminiscent of the situation in humans, where there is variability between individuals and ethnic groups concerning whether, and at what point, obesity-associated complications occur.
“It is clear, therefore, that a better understanding of equine obesity and its related conditions is required,” they said.
The authors say the evidence that genetics influence the development of equine obesity comes from the recognition that breed and “type” are clear risk factors, with ponies at highest risk, followed by cob type breeds.
Breed, they said, is a well-recognised risk factor for EMS.
Evidence points to the heritability of several traits known to be perturbed by EMS (glucose, insulin, measures of insulin sensitivity, and dyslipidaemia).
For dogs, cats, and horses, Wall and Raffan compared the similarities in obesity pathophysiology to humans and reviewed the genetic studies previously reported in those species. In humans, they provided an overview of how genes linked to obesity in humans.
The pair noted the wealth of research into the genetics of human obesity and its related metabolic perturbations, and the relative paucity of efforts to date in dogs, cats, and horses.
“Consequently, those studying veterinary species have much to learn from human geneticists and those studying laboratory animal models.
“By familiarising ourselves with those fields, there is much scope to fast-track animal studies to provide maximum insight into animal disease.
“Fortunately,” they continued, “the flow of information between species need not be along a one-way street.
“Genetic studies of animal disease have already been informative to human research, and there is much potential to discover more.”
They concluded: “The obesity epidemic is a major health concern in both human and companion animals, and there is a lot more to be discovered regarding the molecular basis of obesity and associated metabolic conditions.
“Despite clear evidence that obesity and related traits are highly heritable in companion animals, there are only limited studies to date investigating which genes are responsible and how they exert their effect.”
As this field matures, it promises tangible benefits for animal populations, they said.
Wallis, N.; Raffan, E. The Genetic Basis of Obesity and Related Metabolic Diseases in Humans and Companion Animals. Genes 2020, 11, 1378.