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Hypothalamic eIF2α signaling regulates food intake.



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Maurin, Anne-Catherine 
Benani, Alexandre 
Lorsignol, Anne 
Brenachot, Xavier 
Parry, Laurent 


The reversible phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) is a highly conserved signal implicated in the cellular adaptation to numerous stresses such as the one caused by amino acid limitation. In response to dietary amino acid deficiency, the brain-specific activation of the eIF2α kinase GCN2 leads to food intake inhibition. We report here that GCN2 is rapidly activated in the mediobasal hypothalamus (MBH) after consumption of a leucine-deficient diet. Furthermore, knockdown of GCN2 in this particular area shows that MBH GCN2 activity controls the onset of the aversive response. Importantly, pharmacological experiments demonstrate that the sole phosphorylation of eIF2α in the MBH is sufficient to regulate food intake. eIF2α signaling being at the crossroad of stress pathways activated in several pathological states, our study indicates that hypothalamic eIF2α phosphorylation could play a critical role in the onset of anorexia associated with certain diseases.



Animals, Arcuate Nucleus of Hypothalamus, Eating, Eukaryotic Initiation Factor-2, Gene Knockdown Techniques, Hypothalamus, Leucine, Male, Mice, Mice, Inbred C57BL, Phosphorylation, Protein Serine-Threonine Kinases, Signal Transduction

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Cell Rep

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Elsevier BV
Wellcome Trust (084812/Z/08/Z)
This work was supported by grants from “Fondation pour la Recherche Médicale,” “Société Française de Nutrition,” Ajinomoto Amino Acid Research Program (3ARP), and “Agence Nationale pour la Recherche.”