Dysfunctions of leptin, ghrelin, BDNF and endocannabinoids in eating disorders: Beyond the homeostatic control of food intake

A large body of literature documents the occurrence of alterations in the physiology of both central and peripheral modulators of appetite in acute patients with anorexia nervosa (AN) and bulimia nervosa (BN). Until more recently the role of most of the appetite modulators in the control of eating behavior was conceptualized solely in terms of their influence on homeostatic control of energy balance. However, it is becoming more and more evident that appetite modulators also affect the non-homeostatic cognitive, emotional and rewarding component of food intake as well as non food-related reward, and, recently, AN and BN have been pathophysiologically linked to dysfunctions of reward mechanisms. Therefore, the possibility exists that observed changes in appetite modulators in acute AN and BN may represent not only homeostatic adaptations to malnutrition, but also contribute to the development and/or the maintenance of aberrant non-homeostatic behaviors, such as self-starvation and binge eating. In the present review, the evidences supporting a role of leptin, ghrelin, brain-derived neurotrophic factor and endocannabinoids in the homeostatic and non-homeostatic dysregulations of patients with AN and BN will be presented. The reviewed literature is highly suggestive that changes in the physiology of these modulators may play a pivotal role in the pathophysiology of eating disorders by providing a possible link between motivated behaviors, reward processes, cognitive functions and energy balance.