Vagal afferent controls of feeding: a possible role for gastrointestinal BDNF

Abstract

Vagal gastrointestinal (GI) afferents do not appear to contribute to long-term controls of feeding, despite downstream connections that could support such a role. This view is largely attributable to a lack of evidence for long-term effects, especially the failure of vagal afferent lesions to produce hyperphagia or obesity. Here, the possibility is evaluated that "side effects" of vagal lesion methods resulting largely from complexities of vagal organization would probably suppress long-term effects. Criteria based on knowledge of vagal organization were utilized to critique and compare vagal lesion methods and to interpret their effects on GI function, feeding and body weight. This analysis suggested that it was premature to eliminate a long-term vagal GI afferent role based on the effects of these lesions and highlighted aspects of vagal organization that must be addressed to reduce the problematic side effects of vagal lesions. The potential of "genetic" lesions that alter vagal sensory development to address these aspects, examination of the feasibility of this approach, and the properties of brain-derived neurotrophic factor (BDNF) that made it an attractive candidate for application of this approach are described. BDNF knockout from GI smooth muscle unexpectedly demonstrated substantial overeating and weight gain associated with increased meal size and frequency. The decay of eating rate during a scheduled meal was also reduced. However, meal-induced c-Fos activation was increased in the dorsal motor nucleus of the vagus, suggesting that the effect on eating rate was due to augmentation of GI reflexes by vagal afferents or other neural systems.