6533b86dfe1ef96bd12c968c
RESEARCH PRODUCT
Hypothalamic eIF2 alpha signaling regulates food intake
Yuki MuranishiXavier BrenachotWafa B'chirLuc PénicaudAlexandre BenaniValérie CarraroAnne-catherine MaurinCédric ChaverouxJulien AverousDavid RonAlain BruhatPierre FafournouxCéline JousseLaurent ParryChristophe GuissardAnne Lorsignolsubject
Male[ SDV.AEN ] Life Sciences [q-bio]/Food and NutritionEukaryotic Initiation Factor-2neuronsEatingMicepiriform cortex0302 clinical medicineGene Knockdown Techniquesarcuate nucleusamino-acid deficiency;arcuate nucleus;translational control;energy homeostasis;piriform cortex;cancer cachexia;protein-intake;transfer-rna;mechanism;neuronsPhosphorylationlcsh:QH301-705.52. Zero hungerchemistry.chemical_classification0303 health sciencesGene knockdownalimentationtranslational controlamino-acid deficiencyEukaryotic Initiation Factor-2Amino acidtransfer-rnaGene Knockdown TechniquesAlimentation et NutritionPhosphorylation[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Signal transductionmedicine.symptomSignal Transductioncancer cachexiamedicine.medical_specialtyCellular adaptationHypothalamusmechanismAnorexiaBiologyProtein Serine-Threonine KinasesGeneral Biochemistry Genetics and Molecular BiologyArticle03 medical and health sciencesLeucineInternal medicinemedicineFood and NutritionAnimalsenergy homeostasis030304 developmental biologyNeurosciencesArcuate Nucleus of Hypothalamusprotein-intakeMice Inbred C57BL[SDV.AEN] Life Sciences [q-bio]/Food and NutritionEndocrinologychemistrylcsh:Biology (General)Neurons and Cognition[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition030217 neurology & neurosurgerydescription
International audience; 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-21 |