AMP-activated kinase links serotonergic signaling to glutamate release for regulation of feeding behavior in C. elegans

Cell Metab. 2012 Jul 3;16(1):113-21. doi: 10.1016/j.cmet.2012.05.014.

Abstract

Serotonergic regulation of feeding behavior has been studied intensively, both for an understanding of the basic neurocircuitry of energy balance in various organisms and as a therapeutic target for human obesity. However, its underlying molecular mechanisms remain poorly understood. Here, we show that neural serotonin signaling in C. elegans modulates feeding behavior through inhibition of AMP-activated kinase (AMPK) in interneurons expressing the C. elegans counterpart of human SIM1, a transcription factor associated with obesity. In turn, glutamatergic signaling links these interneurons to pharyngeal neurons implicated in feeding behavior. We show that AMPK-mediated regulation of glutamatergic release is conserved in rat hippocampal neurons. These findings reveal cellular and molecular mediators of serotonergic signaling.

Publication types

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

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cells, Cultured
  • Chemoreceptor Cells / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Feeding Behavior*
  • Gastrointestinal Motility
  • Glutamic Acid / metabolism*
  • Hippocampus / cytology
  • Pharynx / innervation
  • Pharynx / metabolism
  • Pharynx / physiology
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Rats
  • Receptors, Serotonin / metabolism
  • Serotonergic Neurons / enzymology
  • Serotonergic Neurons / metabolism
  • Serotonin / metabolism
  • Synaptic Transmission*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Caenorhabditis elegans Proteins
  • Receptors, Serotonin
  • Serotonin
  • Glutamic Acid
  • Protein Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • AAK-2 protein, C elegans
  • AMP-Activated Protein Kinases