Liver-derived ceramides link metabolism to tissue wasting in cancer cachexia.

Abstract

Cancer cachexia, characterized by weight loss, muscle wasting, and anorexia, complicates cancer treatment and adversely affects patient outcomes. Both tumor-derived and host inflammatory factors are implicated in aspects of cachexia. The search for circulating mediators of cancer cachexia has focused largely on secreted proteins, but metabolites may also drive systemic wasting. In this issue, Morigny, Rohm, and colleagues identified the liver as a major source of circulating ceramides in cachectic mice and patients with cancer and demonstrated that inhibiting ceramide synthesis attenuated muscle wasting and preserved function in cachectic mice. These findings position the liver as an endocrine organ in cachexia and introduce a druggable metabolic pathway with translational potential.