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Publication : Hypothalamic eIF2α signaling regulates food intake.

First Author  Maurin AC Year  2014
Journal  Cell Rep Volume  6
Issue  3 Pages  438-44
PubMed ID  24485657 Mgi Jnum  J:208777
Mgi Id  MGI:5565024 Doi  10.1016/j.celrep.2014.01.006
Citation  Maurin AC, et al. (2014) Hypothalamic eIF2alpha signaling regulates food intake. Cell Rep 6(3):438-44
abstractText  The reversible phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) 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 eIF2alpha 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 eIF2alpha in the MBH is sufficient to regulate food intake. eIF2alpha signaling being at the crossroad of stress pathways activated in several pathological states, our study indicates that hypothalamic eIF2alpha phosphorylation could play a critical role in the onset of anorexia associated with certain diseases.
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