Neural: Mediation of food aversions and anorexia induced by tumor necrosis factor and tumors

Abstract

Tumors often cause declines in food intake and body weight, a condition referred to as tumor anorexia. A macrophagederived peptide known as tumor necrosis factor (TNF) has been proposed as an important mediator of cancer anorexia and cachexia. Our work with an animal model of this condition indicates that strong learned aversions to the available diet arise in rats bearing implanted tumors and that these aversions contribute significantly to depressions in food intake and body weight. Lesions of the area postrema and nearby caudal medial nucleus of the solitary tract (APcmNTS) markedly attenuate both the learned aversions and the anorexia induced by tumor growth. A strikingly similar pattern of effects on tumor-induced aversions and anorexia was seen after subdiaphragmatic vagotomy and after capsaicin treatments. The similarity in the effects of all three treatments suggests that they involve interruption of the same system, presumably afferent signals conveyed by the vagus nerve to the nucleus of the solitary tract. The extent to which peripheral TNF administration generates symptoms similar to those produced by tumor growth was also examined. TNF administration was associated with the development of strong aversions to a novel but not a familiar diet. Area postrema lesions were found to significantly attenuate the effects of TNF on novel diet intake and preference. These observations provide parallels between the effects of TNF and the effects of tumor growth on diet aversions and food intake.