Coordinated regulation of foraging and metabolism in C. elegans by RFamide neuropeptide signaling

Cell Metab. 2009 Apr;9(4):375-85. doi: 10.1016/j.cmet.2009.02.003.


Animals modify food-seeking behavior and metabolism according to perceived food availability. Here we show that, in the roundworm C. elegans, release of neuropeptides from interneurons that are directly postsynaptic to olfactory, gustatory, and thermosensory neurons coordinately regulates behavior and metabolism. Animals lacking these neuropeptides, encoded by the flp-18 gene, are defective in chemosensation and foraging, accumulate excess fat, and exhibit reduced oxygen consumption. Two G protein-coupled receptors of the NPY/RFamide family, NPR-4 and NPR-5, are activated by FLP-18 peptides in vitro and exhibit mutant phenotypes that recapitulate those of flp-18 mutants. Our data suggest that sensory input can coordinately regulate behavior and metabolism via NPY/RFamide-like receptors. They suggest that peptidergic feedback from interneurons regulates sensory neuron activity, and that at least some of this communication occurs extrasynaptically. Extrasynaptic neuropeptide signaling may greatly increase the computational capacity of neural circuits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism
  • Feeding Behavior*
  • Interneurons / cytology
  • Interneurons / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / cytology
  • Lipid Metabolism
  • Models, Biological
  • Mutation / genetics
  • Neuropeptide Y / metabolism
  • Neuropeptides / metabolism*
  • Odorants
  • Organ Specificity
  • Peptides / metabolism
  • Phenotype
  • Receptors, Cell Surface / metabolism
  • Signal Transduction*
  • Xenopus


  • Caenorhabditis elegans Proteins
  • Neuropeptide Y
  • Neuropeptides
  • Peptides
  • Receptors, Cell Surface
  • arginylphenylalaninamide