Biomarkers of vulnerability to pathological body weight loss in a rat model of anorexia nervosa

Anorexia Nervosa (AN) has a mortality rate 12 times higher than the annual death rate from all causes in females aged 15 to 24. Currently, there is no effective treatment for AN, and there is little consensus about the antecedents and triggers that lead to the development of this debilitating disorder. What is becoming apparent is that an interaction between genetic, behavioural and immunological factors may predispose some individuals to AN. The challenge is to take these observations made in humans and rigorously dissect what underlies them in experimental animal models, where predisposing factors can be manipulated in order to interrogate anorexic behaviour. The most well-accepted animal model of AN, known as activity-based anorexia (ABA), exploits the innate motivation of laboratory rats to run in wheels. When rats with access to running wheels are placed on a restricted feeding schedule, there is a paradoxical increase in running activity despite substantially decreased caloric intake, causing a profound reduction in body weight. Our recent work has revealed that nearly one-third of rats are resistant to body weight loss in the ABA paradigm. This under-reported feature of the model, initially seen as an impediment to the generation of “clean” data, we now see as a compelling reason to develop ABA as a translational model of anorexia nervosa. We believe strongly, as do many others, that it is the variability of responses to physiological challenges and the interrogation of the mechanisms that underlie this variability that will inform the development of more effective treatment strategies. This project will focus on identifying biomarkers of vulnerability to ABA and examining their underlying mechanisms with a view to aiding in the early detection and diagnosis of human AN.