To eat or not to eat: A role for ghrelin and LEAP2 in eating disorders?

Abstract

Ghrelin is an orexigenic hormone that orchestrates many diverse behaviours of relevance for feeding control. It appears to operate as a hunger hormone, organizing food intake into meals and ensuring that we seek out and consume a variety of foods. With this physiological biography, the ghrelin system, including the pathways through which it operates, has been interrogated for its role in the aetiology, pathology and treatment of eating disorders. While common obesity does not appear to be a hyperghrelinemic state, it would be difficult to completely rule out enhanced ghrelin signalling. At the other end of the body weight spectrum, it can be questioned whether patients suffering from anorexia nervosa develop ghrelin resistance and/or have high levels of LEAP2, an endogenous antagonist for GHSR, since they do not eat despite having high ghrelin levels. The purpose of this review is to outline gaps in knowledge in the ghrelin field, including in the context of eating disorders.

Keywords: Agouti-related peptide; Anorexia nervosa; Eating disorders; Ghrelin; LEAP2; Obesity; Reward system.

Fig. 1

The “yin-yang” effects of ghrelin and LEAP2, two sensors that bridge metabolism, cognitive processes and eating behaviour through central action on neurones bearing the ghrelin receptor (GHSR). Dysfunctional ghrelin/LEAP2 balance might be key determinant in the pathophysiology of eating disorders such as anorexia nervosa or binge-eating/hyperphagia induced obesity.