The causes of cachexia: key signals and the brain.

Cachexia is a multisystem, complex disorder of body weight and body composition characterized by a relentless, non-resolving wasting of metabolic reserve that, although long recognized and described, continues to elude effective treatment. A continued focus on central nervous system pathways as key drivers of some of the cardinal features of cachexia now points towards the development of long-needed effective interventions. In this Review, we focus on several key signals, namely growth differentiation factor 15, melanocortins and interleukin-6, that illustrate the power of cross-disciplinary thinking to better understand how humoral signals affect body composition, behaviour and cognition in cachexia.