Format

Send to

Choose Destination
Cell Rep. 2014 Feb 13;6(3):438-44. doi: 10.1016/j.celrep.2014.01.006. Epub 2014 Jan 30.

Hypothalamic eIF2α signaling regulates food intake.

Author information

1
UMR 1019 Nutrition Humaine, INRA, Université Clermont 1, Centre de Clermont-Ferrand-Theix, 63122 Saint Genès Champanelle, France.
2
Centre des Sciences du Goût et de l'Alimentation, UMR 6265-CNRS/1324-INRA, Université de Bourgogne, 21000 Dijon, France.
3
STROMAlab, UMR 5273-CNRS Université Paul Sabatier, EFS, U1031 INSERM, BP 84225, 31432 Toulouse Cedex 4, France.
4
University of Cambridge, Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Center, Cambridge CB2 0QQ, UK.
5
UMR 1019 Nutrition Humaine, INRA, Université Clermont 1, Centre de Clermont-Ferrand-Theix, 63122 Saint Genès Champanelle, France. Electronic address: pierre.fafournoux@clermont.inra.fr.

Abstract

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.

PMID:
24485657
PMCID:
PMC4876923
DOI:
10.1016/j.celrep.2014.01.006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center