6533b83afe1ef96bd12a7a94
RESEARCH PRODUCT
Importance of mitochondrial dynamin-related protein 1 in hypothalamic glucose sensitivity in rats.
Luc PénicaudXavier FioramontiMichel RigouletChristophe GuissardPascale BelenguerEmmanuelle NédélecDanielle BailbeCamille AllardCorinne BarreauGéraldine OfferCécile Tourrel-cuzinBénédicte SalinCorinne LeloupLionel Carneirosubject
MaleEnergy-Generating Resourcesnervous-systemPhysiology[ SDV.AEN ] Life Sciences [q-bio]/Food and NutritionClinical BiochemistryneuronsMitochondrionBiochemistryinvolvementEnergy homeostasisDNM1L0302 clinical medicineInsulin-Secreting CellsInsulin SecretionInsulinGeneral Environmental Science2. Zero hungerchemistry.chemical_classification0303 health sciencesTransport proteinMitochondriaProtein TransportHypothalamusGene Knockdown TechniquesMitochondrial MembranesMitochondrial fissionRNA InterferenceDynaminsmedicine.medical_specialtyendocrine systembrainmechanismCarbohydrate metabolismBiology03 medical and health sciencesOxygen ConsumptionInternal medicineexpressionmedicineAnimalsRats WistarMolecular Biologyenergy homeostasis030304 developmental biologyReactive oxygen speciesAppetite RegulationArcuate Nucleus of HypothalamusCell Biologyislet blood-flowRatsEndocrinologyGlucosechemistryVentromedial Hypothalamic NucleusGeneral Earth and Planetary SciencesactivationReactive Oxygen Species[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition030217 neurology & neurosurgeryinsulin-secretiondescription
International audience; AIMS: Hypothalamic mitochondrial reactive oxygen species (mROS)-mediated signaling has been recently shown to be involved in the regulation of energy homeostasis. However, the upstream signals that control this mechanism have not yet been determined. Here, we hypothesize that glucose-induced mitochondrial fission plays a significant role in mROS-dependent hypothalamic glucose sensing. RESULTS: Glucose-triggered translocation of the fission protein dynamin-related protein 1 (DRP1) to mitochondria was first investigated in vivo in hypothalamus. Thus, we show that intracarotid glucose injection induces the recruitment of DRP1 to VMH mitochondria in vivo. Then, expression was transiently knocked down by intra-ventromedial hypothalamus (VMH) DRP1 siRNA (siDRP1) injection. 72 h post siRNA injection, brain intracarotid glucose induced insulin secretion, and VMH glucose infusion-induced refeeding decrease were measured, as well as mROS production. The SiDRP1 rats decreased mROS and impaired intracarotid glucose injection-induced insulin secretion. In addition, the VMH glucose infusion-induced refeeding decrease was lost in siDRP1 rats. Finally, mitochondrial function was evaluated by oxygen consumption measurements after DRP1 knock down. Although hypothalamic mitochondrial respiration was not modified in the resting state, substrate-driven respiration was impaired in siDRP1 rats and associated with an alteration of the coupling mechanism. INNOVATION AND CONCLUSION: Collectively, our results suggest that glucose-induced DRP1-dependent mitochondrial fission is an upstream regulator for mROS signaling, and consequently, a key mechanism in hypothalamic glucose sensing. Thus, for the first time, we demonstrate the involvement of DRP1 in physiological regulation of brain glucose-induced insulin secretion and food intake inhibition. Such involvement implies DRP1-dependent mROS production.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-08-01 |