0000000000231046
AUTHOR
Christophe Guissard
PO39 La fission mitochondriale induite par le glucose est indispensable à la signalisation ROS lors de la détection hypothalamique de l’hyperglycémie
Introduction Nous avons montre que la detection hypothalamique de l’hyperglycemie (HG) fait intervenir une signalisation ROS d’origine mitochondriale, laquelle est indispensable aux reponses effectrices, dont la secretion d’insuline. Par ailleurs, des etudes recentes montrent que la morphologie des mitochondries varie lors de l’HG, morphologie qui est dependante de la dynamique mitochondriale, modifiant alors la production de ROS. Ainsi, l’inhibition de la fission mitochondriale diminue la production de ROS lors d’une hyperglycemie dans l’hepatocyte par exemple. Objectif Comprendre si, in vivo, la signalisation par les ROS lors du « glucose sensing » hypothalamique, implique la dynamique mi…
Importance of mitochondrial dynamin-related protein 1 in hypothalamic glucose sensitivity in rats.
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, expressio…
Fatty Acid Transporter CD36 Mediates Hypothalamic Effect of Fatty Acids on Food Intake in Rats
Subject Areas: carotid arteries; emulsions; fatty acids; gene expression; heparin; hypothalamus; neurons; oxidation.; International audience; Variations in plasma fatty acid (FA) concentrations are detected by FA sensing neurons in specific brain areas such as the hypothalamus. These neurons play a physiological role in the control of food intake and the regulation of hepatic glucose production. Le Foll et al. previously showed in vitro that at least 50% of the FA sensing in ventromedial hypothalamic (VMH) neurons is attributable to the interaction of long chain FA with FA translocase/CD36 (CD36). The present work assessed whether in vivo effects of hypothalamic FA sensing might be partly m…
Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice
International audience; Hormones such as leptin and ghrelin can rapidly rewire hypothalamic feeding circuits when injected into rodent brains. These experimental manipulations suggest that the hypothalamus might reorganize continually in adulthood to integrate the metabolic status of the whole body. In this study, we examined whether hypothalamic plasticity occurs in naive animals according to their nutritional conditions. For this purpose, we fed mice with a short-term high-fat diet (HFD) and assessed brain remodeling through its molecular and functional signature. We found that HFD for 3 d rewired the hypothalamic arcuate nucleus, increasing the anorexigenic tone due to activated pro-opio…
Hypothalamic eIF2 alpha signaling regulates food intake
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 demo…
Glucose-induced mitochondrial fission through DRP1 is required for redox signaling in hypothalamic glucose sensing mechanism
Communication affichée; We previously showed that hypothalamic glucose sensing requires a redox signaling in hypothalamic arcuate nucleus, through glucose‐induced mitochondrial H2O2 production (1). ROS implication in nutrient sensing has been confirmed by others studies (2). Recent studies highlight mitochondrial morphology changes under glycemia increase, which depends on mitochondrial dynamics. Changes in mitochondrial dynamics are causative events in mitochondrial reactive oxygen species (mROS) production when glycemia rises. It has been demonstrates that mitochondrial fission blockade decreases mROS production during hyperglycemia in metabolic‐sensitive cells, such as hepatocytes or myo…