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

AC Maurin, C Jousse, J Averous, L Parry, A Bruhat… - Cell metabolism, 2005 - cell.com
AC Maurin, C Jousse, J Averous, L Parry, A Bruhat, Y Cherasse, H Zeng, Y Zhang…
Cell metabolism, 2005cell.com
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 α (eIF2α) in response to intracellular amino acid deficiency,
impairs this aversive response. GCN2 inactivation also diminishes phosphorylated eIF2α …
Summary
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 α (eIF2α) in response to intracellular amino acid deficiency, impairs this aversive response. GCN2 inactivation also diminishes phosphorylated eIF2α 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.
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