Advances in the understanding of appetite are leading to a refined concept of disease
cachexia and point to novel therapeutic strategies based on the manipulation of appetite. The complex social and psychological short-term influences on appetite obscure the fact that over the longer term appetite is tightly regulated by physiological considerations; the homeostatic control of energy balance. Like
obesity, which is now viewed as a disorder of homeostasis,
cachexia can be seen as an adaptive response to the disease state that becomes harmful when prolonged. Several lines of evidence implicate a disorder of appetite regulation in the pathogenesis of
cachexia. As the only known circulating mediator of increased appetite the
peptide hormone ghrelin has attracted attention as a potential
therapy. Trials in patients with various
chronic illnesses, including
cancer and
kidney failure, have demonstrated short-term increases in energy intake. Trials in patients with
emphysema and
heart failure have also shown benefits in clinical outcomes such as lean body mass and exercise capacity, and longer-term trials using oral analogues are being undertaken. As well as improving nutrition,
ghrelin has a number of other actions that may be useful, including an anti-inflammatory effect; of interest since many cachexias are associated with inappropriate immune activation. The manipulation of appetite, in particular by
ghrelin agonism, is emerging as an exciting potential
therapy for disease
cachexia. Future research should focus on the ascertainment of clinically-relevant outcomes, and further characterisation of the non-nutritional effects of this pathway.