Cancer-induced anorexia and malaise are mediated by CGRP neurons in the parabrachial nucleus

Anorexia is a common manifestation of chronic diseases, including cancer. Here we investigate the contribution to cancer anorexia made by calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) that transmit anorexic signals. We show that CGRP^PBN neurons are activated in mice implanted with Lewis lung carcinoma cells. Inactivation of CGRP^PBN neurons before tumor implantation prevents anorexia and loss of lean mass, and their inhibition after symptom onset reverses anorexia. CGRP^PBN neurons are also activated in Apc^min/+ mice, which develop intestinal cancer and lose weight despite the absence of reduced food intake. Inactivation of CGRP^PBN neurons in Apc^min/+ mice permits hyperphagia that counteracts weight loss, revealing a role for these neurons in a 'nonanorexic' cancer model. We also demonstrate that inactivation of CGRP^PBN neurons prevents lethargy, anxiety and malaise associated with cancer. These findings establish CGRP^PBN neurons as key mediators of cancer-induced appetite suppression and associated behavioral changes.