Implication de l’apéline hypothalamique dans la mise en place d’un diabète de type 2 par le contrôle de la production hépatique de glucose via le système nerveux autonome

Détection cérébrale du glucose, plasticité neuronale et métabolisme énergétique

Resume L’apport d’energie est, dans la plupart des cas extremement, bien controle et est ajuste aux depenses d’energie d’un individu donne, c’est ce que l’on nomme l’homeostasie energetique. Cet equilibre repose en grande partie sur la capacite du systeme nerveux central a evaluer le statut energetique de l’organisme, en integrant differents signaux provenant de la peripherie dont le glucose. Cette revue porte sur les decouvertes recentes concernant l’identification des differents mecanismes cellulaires et moleculaires, des types cellulaires et de leur phenotype, des reseaux neuronaux et de leur plasticite. Ainsi il est maintenant etabli qu’il existe differents types de neurones repondant, …

Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes

Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver gluc…

The histone acetyltransferase MOF activates hypothalamic polysialylation to prevent diet-induced obesity in mice

Overfeeding causes rapid synaptic remodeling in hypothalamus feeding circuits. Polysialylation of cell surface molecules is a key step in this neuronal rewiring and allows normalization of food intake. Here we examined the role of hypothalamic polysialylation in the long-term maintenance of body weight, and deciphered the molecular sequence underlying its nutritional regulation. We found that upon high fat diet (HFD), reduced hypothalamic polysialylation exacerbated the diet-induced obese phenotype in mice. Upon HFD, the histone acetyltransferase MOF was rapidly recruited on the St8sia4 polysialyltransferase-encoding gene. Mof silencing in the mediobasal hypothalamus of adult mice prevented…

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…