Abstract
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 regulation of adiposity is a homeostatic process vulnerable to disruption by a multitude of genetic and environmental factors. 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. In this review, we provide an overview of how genes link to obesity in humans, drawing on a wealth of information from laboratory animal models, and summarise the mechanisms by which obesity causes related disease. Throughout, we focus on how large-scale human studies and niche investigations of rare mutations in severely affected patients have improved our understanding of obesity biology and can inform our ability to interpret results of animal studies. For dogs, cats, and horses, we compare the similarities in obesity pathophysiology to humans and review the genetic studies that have been previously reported in those species. Finally, we discuss how veterinary genetics may learn from humans about studying precise, nuanced phenotypes and implementing large-scale studies, but also how veterinary studies may be able to look past clinical findings to mechanistic ones and demonstrate translational benefits to human research.
Highlights
Obesity presents a major health problem in humans and companion animals alike
Brain-derived neurotrophic factor (BDNF) acts on its receptor tropomyosin receptor kinase B (TRKB), and there is increasing evidence that this signalling plays a significant role in sustaining equilibrium of energy balance in the brain [61]
Some of the variation in obesity susceptibility between breeds could be down to differences in “fashion” for each breed, the repeated finding of breed as a risk factor for obesity means genetic determinants are more likely the cause. Such variation in trait susceptibility between breeds is common in dogs due to the species’ unusual population architecture in which there is high diversity as a whole combined with high homogeneity within breeds, the product of population bottlenecks at breed formation and subsequent intensive selection for breed-specific traits [116,117,118]
Summary
Obesity presents a major health problem in humans and companion animals alike. Obesity has commonly been considered a ramification of poor self-control in people or of inept management by animal owners. Considerable evidence shows obesity is better regarded as a disease of disordered energy homeostasis in which a multitude of genetic and environmental factors can contribute to increasing body fat. This review first examines the pathophysiology of obesity and the role of genetics in the disease, focussing on the wealth of evidence from human and rodent studies. Genes 2020, 11, 1378 of obesity and related metabolic disease in companion animals. We consider opportunities for future research in companion animals that may improve understanding of both animal and human obesity
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