The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores.
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.
Maurin
Anne-Catherine
AC
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique de Theix, 63122 Saint Genès-Champanelle, France.
Jousse
Céline
C
Averous
Julien
J
Parry
Laurent
L
Bruhat
Alain
A
Cherasse
Yoan
Y
Zeng
Huiqing
H
Zhang
Yuhong
Y
Harding
Heather P
HP
Ron
David
D
Fafournoux
Pierre
P
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011494:Protein Kinases / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases
D000596:Amino Acids; D015852:Eukaryotic Initiation Factor-2; D011494:Protein Kinases; C070634:Eif2ak4 protein, mouse; D017346:Protein Serine-Threonine Kinases