The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores

Cell Metab. 2005 Apr;1(4):273-7. doi: 10.1016/j.cmet.2005.03.004.


To insure an adequate supply of nutrients, omnivores choose among available food sources. This process is exemplified by the well-characterized innate aversion of omnivores to otherwise nutritious foods of imbalanced amino acid content. We report that brain-specific inactivation of GCN2, a ubiquitously expressed protein kinase that phosphorylates translation initiation factor 2 alpha (eIF2alpha) in response to intracellular amino acid deficiency, impairs this aversive response. GCN2 inactivation also diminishes phosphorylated eIF2alpha levels in the mouse anterior piriform cortex following consumption of an imbalanced meal. An ancient intracellular signal transduction pathway responsive to amino acid deficiency thus affects feeding behavior by activating a neuronal circuit that biases consumption against imbalanced food sources.

Publication types

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

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Eukaryotic Initiation Factor-2 / metabolism
  • Feeding Behavior / physiology*
  • Homeostasis / physiology*
  • Mice
  • Mice, Knockout
  • Phosphorylation
  • Protein Kinases / deficiency
  • Protein Kinases / metabolism
  • Protein Kinases / physiology*
  • Protein-Serine-Threonine Kinases


  • Amino Acids
  • Eukaryotic Initiation Factor-2
  • Protein Kinases
  • Eif2ak4 protein, mouse
  • Protein-Serine-Threonine Kinases