Mitochondrial Dynamin-Related Protein 1 (DRP1) translocation in response to cerebral glucose is impaired in a rat model of early alteration in hypothalamic glucose sensing

OBJECTIVE: Hypothalamic glucose sensing (HGS) initiates insulin secretion (IS) via a vagal control, participating in energy homeostasis. This requires mitochondrial reactive oxygen species (mROS) signaling, dependent on mitochondrial fission, as shown by invalidation of the hypothalamic DRP1 protein. Here, our objectives were to determine whether a model with a HGS defect induced by a short, high fat-high sucrose (HFHS) diet in rats affected the fission machinery and mROS signaling within the mediobasal hypothalamus (MBH). METHODS: Rats fed a HFHS diet for 3 weeks were compared with animals fed a normal chow. Both in vitro (calcium imaging) and in vivo (vagal nerve activity recordings) experiments to measure the electrical activity of isolated MBH gluco-sensitive neurons in response to increased glucose level were performed. In parallel, insulin secretion to a direct glucose stimulus in isolated islets vs. insulin secretion resulting from brain glucose stimulation was evaluated. Intra-carotid glucose load-induced hypothalamic DRP1 translocation to mitochondria and mROS (H2O2) production were assessed in both groups. Finally, compound C was intracerebroventricularly injected to block the proposed AMPK-inhibited DRP1 translocation in the MBH to reverse the phenotype of HFHS fed animals. RESULTS: Rats fed a HFHS diet displayed a decreased HGS-induced IS. Responses of MBH neurons to glucose exhibited an alteration of their electrical activity, whereas glucose-induced insulin secretion in isolated islets was not affected. These MBH defects correlated with a decreased ROS signaling and glucose-induced translocation of the fission protein DRP1, as the vagal activity was altered. AMPK-induced inhibition of DRP1 translocation increased in this model, but its reversal through the injection of the compound C, an AMPK inhibitor, failed to restore HGS-induced IS. CONCLUSIONS: A hypothalamic alteration of DRP1-induced fission and mROS signaling in response to glucose was observed in HGS-induced IS of rats exposed to a 3 week HFHS diet. Early hypothalamic modifications of the neuronal activity could participate in a primary defect of the control of IS and ultimately, the development of diabetes.Rôle des connexines astrocytaires dans le mécanisme de détection hypothalamique du glucose : implication sur le contrôle nerveux du métabolisme énergétiqu

Postprandial hyperglycemia stimulates neuroglial plasticity in hypothalamic POMC neurons after a balanced meal

Mechanistic studies in rodents evidenced synaptic remodeling in neuronal circuits that control food intake. However, the physiological relevance of this process is not well defined. Here, we show that the firing activity of anorexigenic POMC neurons located in the hypothalamus is increased after a standard meal. Postprandial hyperactivity of POMC neurons relies on synaptic plasticity that engages pre-synaptic mechanisms, which does not involve structural remodeling of synapses but retraction of glial coverage. These functional and morphological neuroglial changes are triggered by postprandial hyperglycemia. Chemogenetically induced glial retraction on POMC neurons is sufficient to increase POMC activity and modify meal patterns. These findings indicate that synaptic plasticity within the melanocortin system happens at the timescale of meals and likely contributes to short-term control of food intake. Interestingly, these effects are lost with a high-fat meal, suggesting that neuroglial plasticity of POMC neurons is involved in the satietogenic properties of foods.Contrôle nerveux de la prise alimentaire et du métabolisme par une molécule neurale d'adhésion cellulaireISITE " BFCRéseau d'Innovation sur les Voies de Signalisation en Sciences de la Vi

The neural feedback loop between the brain and adipose tissues

Communication également publiée dans le livre "Adipose tissue development: from animal models to clinical conditions" (ISBN 978-3-8055-9450-9) de C. Levy-Marchal et L. Pénicaud (eds)There are more and more data supporting the importance of nervous regulation of both white and brown adipose tissue mass. This short paper will review the different physiological parameters which are regulated such as metabolism (lipolysis and thermogeneis), secretory activity (leptin and other adipokines) but also to plasticity of adipose tissues (proliferation differentiation and apoptosis). The sensory innervation of white adipose issue and its putative role will be also described. Altogether these results showed the presence of a neural feedback loop between adipose tissues and the brain which plays a major role in the regulation of energy homeostasis and has been shown to be altered in physiologic as well as in metabolic pathologies

Influence des expériences sensorielles précoces sur le comportement alimentaire

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Contrôle du métabolisme intermédiaire par les systèmes nerveux central et périphérique

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Biology of food intake [Session II: Promising fields in the science of nutrition / Food dedicated to human health]

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Reactive oxygen species and nutrient sensing

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Brain-white adipose tissue relationship: Early features

Editeur commercial : ECOG’s eBook on Child and Adolescent ObesityCentral and autonomic nervous systems are involved in the regulation of whole body energy by regulating its different components: intake, expenditure and storage. The different functions (metabolic, secretory, plasticity) of adipose tissues are indeed deeply controlled by the autonomic nervous system. In most mammals, two types of adipose tissue, white and brown, are present. Both are able to store energy in the form of triacylglycerols and to hydrolyze them into free fatty acids and glycerol. Whereas white adipose tissue (WAT) provide lipids as substrates for other tissues, brown adipose tissue (BAT) uses fatty acids for heat production. Over a period of time, white fat mass reflects the balance between energy expenditure and energy intake. Remarkably body fat mass remains relatively constant in adult suggesting that food intake and energy expenditure are linked. This has been supported by numerous studies that demonstrated the inter-dependency of these parameters and thus a feedback loop between the brain and adipose tissues with the involvement of the autonomic nervous system on one side and that of sensory fibers and metabolites or hormonal signals on the other

Importance du transporteur de glucose insulinosensible glut4 dans le système nerveux central (rôles physiologiques et mécanismes cellulaires)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Influence des expériences sensorielles précoces sur le comportement alimentaire

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