Genetic Identification of Vagal Sensory Neurons That Control Feeding

Cell. 2019 Nov 14;179(5):1129-1143.e23. doi: 10.1016/j.cell.2019.10.031.


Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive cues, but the identity of the key sensory neurons and corresponding signals that regulate food intake remains unknown. Here, we use an approach for target-specific, single-cell RNA sequencing to generate a map of the vagal cell types that innervate the gastrointestinal tract. We show that unique molecular markers identify vagal neurons with distinct innervation patterns, sensory endings, and function. Surprisingly, we find that food intake is most sensitive to stimulation of mechanoreceptors in the intestine, whereas nutrient-activated mucosal afferents have no effect. Peripheral manipulations combined with central recordings reveal that intestinal mechanoreceptors, but not other cell types, potently and durably inhibit hunger-promoting AgRP neurons in the hypothalamus. These findings identify a key role for intestinal mechanoreceptors in the regulation of feeding.

Keywords: AgRP Neurons; RNA sequencing; chemogenetics; fiber photometry; hypothalamus; optogenetics; satiation; stretch; vagal afferents; vagus nerve.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / metabolism
  • Animals
  • Brain / physiology
  • Feeding Behavior / physiology*
  • Gastrointestinal Tract / innervation
  • Genetic Markers
  • Genetic Phenomena*
  • Mechanoreceptors / metabolism
  • Mice
  • Sensory Receptor Cells / physiology*
  • Vagus Nerve / anatomy & histology
  • Vagus Nerve / physiology*
  • Viscera / innervation


  • Agouti-Related Protein
  • Agrp protein, mouse
  • Genetic Markers