Anorexia in cancer: role of feeding-regulatory peptides

Abstract

Anorexia is one of the most common symptoms in advanced cancer and is a frequent cause of discomfort for cancer patients and their families. The pathogenesis of cancer anorexia is multi-factorial and involves most of the hypothalamic neuronal signalling pathways modulating energy homeostasis. It is considered to be the result of a failure of usual appetite and satiety signals. Loss of appetite can arise from decreased taste and smell of food, as well as from dysfunctional hypothalamic signalling pathways and cytokine production. Cytokines in particular, appear to play a key role in energy balance through persistent activation of the melanocortin system and inhibition of the neuropeptide Y pathway. The imbalance between anorexigenic and orexigenic peptides leads to suppression of appetite, and increased satiety and satiation associated with marked weight loss and decline in physical performance. High levels of serotonin also appear to contribute to these effects and recent findings implicate corticotropin-releasing factor in the pathogenesis of cancer anorexia as well. Despite significant advances in our understanding of the regulation of food intake and energy expenditure, few effective therapies are available. A better appreciation of the molecular and neuronal mechanisms that control body weight homeostasis may lead to the development of new therapies for improving the survival and quality of life of these patients.

Figure 1

Schematic mechanism of the regulation of the feeding in cancer patients. Reduced fat stores, gut hormones and sensory signals inform CNS about energy balance and food preferences. Pro-inflammatory cytokines and serotonin interact in the CNS inducing anorexia and satiety. In the hypothalamus, increased levels of cytokines play a role activating the anorexigenic pathways and inhibiting the orexigenic pathways. Pro-inflammatory cytokines seem to increase the serotonin concentrations, which amplify the catabolic effects of cytokines and induce satiety. The white arrows show stimulatory input whereas the dashed arrows show anorexigic input. POMC, proopiomelanocortin peptide; NPY, neuropeptide Y; ARC, arcuate nucleus of the hypothalamus; PVN, paraventricular nucleus of the hypothalamus; GUT, gastrointestinal tract; CNS, central nervous system.