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Hypothalamic eIF2 alpha signaling regulates food intake

Abstract : The reversible phosphorylation of the a subunit of eukaryotic initiation factor 2 (eIF2 alpha) 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 eIF2 alpha 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 eIF2 alpha in the MBH is sufficient to regulate food intake. eIF2 alpha signaling being at the crossroad of stress pathways activated in several pathological states, our study indicates that hypothalamic eIF2 alpha phosphorylation could play a critical role in the onset of anorexia associated with certain diseases.
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Anne-Catherine Maurin, Alexandre Benani, Anne Lorsignol, Xavier Brenachot, Laurent Parry, et al.. Hypothalamic eIF2 alpha signaling regulates food intake. Cell Reports, Elsevier Inc, 2014, 6 (3), pp.438-444. ⟨10.1016/j.celrep.2014.01.006⟩. ⟨hal-02635326⟩

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