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

Quand notre intestin parle à notre cerveau...

Une alimentation maternelle enrichie en gras pendant la gestation et l’allaitement oriente le nouveau-né vers un lait produit sous régime gras (modèle murin)

Insulin differently modulates hypothalamic mitochondrial energy metabolism in fed or fasted mice: Involvement in food intake regulation?

0195-6663 doi: DOI: 10.1016/j.appet.2008.04.119; In hypothalamus, mitochondria have been demonstrated to be involved in nutrients sensing but little is known concerning a mitochondrial insulin effect. The aim of our studywas thus to determine, in mice, whether (i) insulin may modulate mitochondrial functions and (ii) this effect varies according to metabolic state. O2 consumption, measured by oxygraphy in fresh hypothalamus explants was similar in fed and fasted mice on glutamate whereas it was lower in fasted mice on succinate. Whatever the metabolic state of the mice, insulin (3 nM) increased O2 consumption with glutamate. By contrast, insulin increased O2 consumption with succinate only …

Hypothalamus-olfactory system crosstalk: orexin a immunostaining in mice

It is well known that olfaction influences food intake, and conversely, that an individual’s nutritional status modulates olfactory sensitivity. However, what is still poorly understood is the neuronal correlate of this relationship, as well as the connections between the olfactory bulb and the hypothalamus. The goal of this report is to analyze the relationship between the olfactory bulb and hypothalamus, focusing on orexin A immunostaining, a hypothalamic neuropeptide that is thought to play a role in states of sleep/wakefulness. Interestingly, orexin A has also been described as a food intake stimulator. Such an effect may be due in part to the stimulation of the olfactory bulbar pathway…

Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signalling

1939-327X (Electronic) Journal article; Objective : Recent data demonstrate that glucose sensing in different tissues is initiated by an intracellular redox-signaling pathway in physiological conditions. However, the relevance of such a mechanism in metabolic disease is not known. The aim of the present study was to determine whether brain-glucose hypersensitivity present in obese Zucker rat is related to an alteration in redox signaling. Research design and Methods: Brain glucose sensing alteration was investigated in vivo through the evaluation of electrical activity in arcuate nucleus, changes in ROS levels, and hypothalamic glucose-induced insulin secretion. In basal conditions, modific…

Chicken adaptive response to low energy diet: main role of the hypothalamic lipid metabolism revealed by a phenotypic and multi-tissue transcriptomic approach

AbstractBackgroundProduction conditions of layer chicken can vary in terms of temperature or diet energy content compared to the controlled environment where pure-bred selection is undertaken. The aim of this study was to better understand the long-term effects of a 15%-energy depleted diet on egg-production, energy homeostasis and metabolism via a multi-tissue transcriptomic analysis. Study was designed to compare effects of the nutritional intervention in two layer chicken lines divergently selected for residual feed intake.ResultsChicken adapted to the diet in terms of production by significantly increasing their feed intake and decreasing their body weight and body fat composition, whil…

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, …

Crosstalk between hypothalamic neurons and olfactory system: a tracing and anatomo-fuctional investigation in mouse

A table ! Voyage au cœur des habitudes alimentaires

En collaboration avec Science en Lumière (CNRS et Université de Lorraine), le Jardin des Sciences de Dijon, l’uB ( Mission Culture Scientifique), le CSGA organise une projection du film-documentaire « A table » suivi d’une conférence-débat avec 2 chercheurs du CSGA, Sandrine Monnery-Patris et Laurent Brondel. Le débat sera animé Alexandre Benani (CSGA) et Véronique Bronner (CNRS/Univ. de Lorraine). Sur inscription (dans la limite des places disponibles) au 03.80.48.82.00

Evaluation of the 26RFa/GPR103 peptidergic system in a mouse model of insulinopenia

International audience

Toward a link between brain plasticity and satiety

International audience

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…

Apelin treatment increases complete Fatty Acid oxidation, mitochondrial oxidative capacity, and biogenesis in muscle of insulin-resistant mice.

Both acute and chronic apelin treatment have been shown to improve insulin sensitivity in mice. However, the effects of apelin on fatty acid oxidation (FAO) during obesity-related insulin resistance have not yet been addressed. Thus, the aim of the current study was to determine the impact of chronic treatment on lipid use, especially in skeletal muscles. High-fat diet (HFD)-induced obese and insulin-resistant mice treated by an apelin injection (0.1 μmol/kg/day i.p.) during 4 weeks had decreased fat mass, glycemia, and plasma levels of triglycerides and were protected from hyperinsulinemia compared with HFD PBS-treated mice. Indirect calorimetry experiments showed that apelin-treated mice…

Role for mitochondrial reactive oxygen species in brain lipid sensing: redox regulation of food intake.

0012-1797 (Print) Journal Article Research Support, Non-U.S. Gov't; The ability for the brain to sense peripheral fuel availability is mainly accomplished within the hypothalamus, which detects ongoing systemic nutrients and adjusts food intake and peripheral metabolism as needed. Here, we hypothesized that mitochondrial reactive oxygen species (ROS) could trigger sensing of nutrients within the hypothalamus. For this purpose, we induced acute hypertriglyceridemia in rats and examined the function of mitochondria in the hypothalamus. Hypertriglyceridemia led to a rapid increase in the mitochondrial respiration in the ventral hypothalamus together with a transient production of ROS. Cerebral…

Intégration centrale de la perception sensorielle associée à l’alimentation

Poster; National audience

The neuropeptide 26RFa (QRFP) is a key regulator of glucose homeostasis and its activity is markedly altered in obese/hyperglycemic mice

International audience; Recent studies have shown that the hypothalamic neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin, and increasing insulin sensitivity. In this study, we further characterized the role of the 26RFa/GPR103 peptidergic system in the global regulation of glucose homeostasis using a 26RFa receptor antagonist, and also assessed whether a dysfunction of the 26RFa/GPR103 system occurs in obese hyperglycemic mice. Firstly, we demonstrate that administration of the GPR103 antagonist reduces the global glucose-induced incretin effect and insulin sensitivity whereas, conversely, administration of exogenous 26RFa attenuates glucose-induced hyperglycemia. U…

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…

Un traitement chronique à l'apeline chez la souris obèse et résistante à l'insuline augmente l'oxydation des acides gras et la biogénèse mitochondriale dans le muscle

Communication orale ; http://www.lesjfn.fr

The neuropeptide 26RFa in the human gut and pancreas: potential involvement in glucose homeostasis

Objective Recent studies performed in mice revealed that the neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity. However, in humans, an association between 26RFa and the regulation of glucose homeostasis is poorly documented. In this study, we have thus investigated in detail the distribution of 26RFa and its receptor, GPR103, in the gut and the pancreas, and determined the response of this peptidergic system to an oral glucose challenge in obese patients. Design and methods Distribution of 26RFa and GPR103 was examined by immunohistochemistry using gut and pancreas tissue sections. Circulating 26RFa was determined using a specif…

Comportement alimentaire

National audience

High fat diet rapidly induces brain-plasticity-related transcriptomic signature in hypothalamus: role in energy homeostasis

Poster board E12 (1 page) ; Session 203 - Food intake regulation 3 - Abstract n° 203.1 - Publication ref.: FENS Abstr., vol.5, 203.1, 2010; International audience; We have investigated the early events that are induced by a hypercaloric hyperlipidic diet in mice. The high fat diet rapidly induced metabolic imbalance, as soon as the first day, which is characterized. by a large increase in energy intake and several others metabolic alterations such as. hypercholesterolemia, and glucose intolerance. However, the diet-induced metabolic imbalance was. fully reversed after a week, suggesting that a physiological adaptive response has been then induced,. probably in order to counteract the delete…

Hypothalamic reactive oxygen species are required for insulin-induced food intake inhibition: an NADPH oxidase-dependent mechanism

1939-327X (Electronic) Journal Article Research Support, Non-U.S. Gov't; OBJECTIVE: Insulin plays an important role in the hypothalamic control of energy balance, especially by reducing food intake. Emerging data point to a pivotal role of reactive oxygen species (ROS) in energy homeostasis regulation, but their involvement in the anorexigenic effect of insulin is unknown. Furthermore, ROS signal derived from NADPH oxidase activation is required for physiological insulin effects in peripheral cells. In this study, we investigated the involvement of hypothalamic ROS and NADPH oxidase in the feeding behavior regulation by insulin. RESEARCH DESIGN AND METHODS: We first measured hypothalamic RO…

Centrifugal projections to the main olfactory bulb revealed by trans‐synaptic retrograde tracing in mice

A wide range of evidence indicates that olfactory perception is strongly involved in food intake. However, the polysynaptic circuitry linking the brain areas involved in feeding behavior to the olfactory regions is not well known. The aim of this article was to examine such circuits. Thus, we described, using hodological tools such as transsynaptic viruses (PRV152) transported in a retrograde manner, the long-distance indirect projections (two to three synapses) onto the main olfactory bulb (MOB). The ß-subunit of the cholera toxin which is a monosynaptic retrograde tracer was used as a control to be able to differentiate between direct and indirect projections. Our tracing experiments show…

Quand notre intestin parle à notre cerveau...

Trois scientifiques interviendront une dizaine de minutes chacun sur les thèmes suivants : • Intestin et humeur, ou les relations entre microbiote, stress et dépression, par le professeur Pierre Déchelotte (CHU de Rouen). • Intestin et maladies métaboliques (obésité, diabète) : l’influence des hormones, par le professeur Claude Knauf (Université de Toulouse) • Intestin et comportement alimentaire : l’influence des nutriments sur les sensations de faim et de satiété, par le docteur Gilles Mithieux (Inserm, Lyon). Suivront 30 à 60 minutes de questions – réponses avec le public.

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…

A high-fat diet increases l-carnitine synthesis through a differential maturation of the Bbox1 mRNAs.

International audience; l-carnitine is a key molecule in both mitochondrial and peroxisomal lipid metabolisms. l-carnitine is biosynthesized from gamma-butyrobetaine by a reaction catalyzed by the gamma-butyrobetaine hydroxylase (Bbox1). The aim of this work was to identify molecular mechanisms involved in the regulation of l-carnitine biosynthesis and availability. Using 3' RACE, we identified four alternatively polyadenylated Bbox1 mRNAs in rat liver. We utilized a combination of in vitro experiments using hybrid constructs containing the Bbox1 3' UTR and in vivo experiments on rat liver mRNAs to reveal specificities in the different Bbox1 mRNA isoforms, especially in terms of polyadenyla…

Une alimentation maternelle enrichie en gras pendant la gestation ou l’allaitement oriente les préférences du souriceau vers un aliment gras à la naissance et au sevrage

Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis

Fil: Chrétien, Chloé. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Fenech, Claire. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Liénard, Fabienne. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Grall, Sylvie. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Chevalier, Charlène. University of …

Exploration fonctionnelle du système neuronal à mélanocortine et corrélats comportementaux chez le rongeur

Le CSGA célèbre la Semaine du Goût

Le Centre des Sciences du Goût et de l'Alimentation (CSGA) célèbre la Semaine du Goût avec au programme : * Projection-débat du film "A table ! Voyage au coeur des aliments" animée par Véronique Bronner, coordinatrice de Sciences en Lumière et Alexandre Benani, chercheur CNRS en neurosciences au CSGA > jeudi 11 octobre 2018 * Journée portes ouvertes du CSGA > samedi 13 octobre 2018 Entrée libre tous publics [u]En savoir plus :[/u] http://www.dijon.inra.fr/Evenements/Semaine-gout-dijon-2018-csga

Pourquoi j'ai encore faim ?

Comment les sensations de faim et de satiété sont produites par notre cerveau ? Quelle zone de notre cerveau va s’activer aux horaires des repas et sur la base de quelles stimulations ? À travers quelques exemples, Alexandre Benani illustrera l’importance du dialogue entre nos organes et notre cerveau dans l’élaboration de ces sensations.

Inactivation of Socs3 in the Hypothalamus Enhances the Hindbrain Response to Endogenous Satiety Signals via Oxytocin Signaling.

Leptin is an adipocyte-derived hormone that controls energy balance by acting primarily in the CNS, but its action is lost in common forms of obesity due to central leptin resistance. One potential mechanism for such leptin resistance is an increased hypothalamic expression of Suppressor of cytokine signaling 3 (Socs3), a feedback inhibitor of the Jak-Stat pathway that prevents Stat3 activation. Ample studies have confirmed the important role of Socs3 in leptin resistance and obesity. However, the degree to which Socs3 participates in the regulation of energy homeostasis in nonobese conditions remains largely undetermined. In this study, using adult mice maintained under standard diet, we d…

Brain Control of Plasma Cholesterol Involves Polysialic Acid Molecules in the Hypothalamus

IF 3.566; International audience; The polysialic acid (PSA) is a large glycan that is added to cell-surface proteins during their post-translational maturation. In the brain, PSA modulates distances between cells and controls the plasticity of the nervous system. In the hypothalamus, PSA is involved in many aspects of energy balance including food intake, osmoregulation, circadian rhythm, and sleep. In this work, we investigated the role of hypothalamic PSA in the regulation of plasma cholesterol levels and distribution. We report that HFD consumption in mice rapidly increased plasma cholesterol, including VLDL, LDL, and HDL-cholesterol. Although plasma VLDL-cholesterol was normalized withi…

Vers un lien entre plasticité du cerveau et satiété

Vous venez de terminer un bon repas et vous vous sentez repu ?Des chercheurs (1) viennent de comprendre des mécanismes qui, dans votre cerveau, ont contribué à cet état. Il s’agit d’une cascade de réactions déclenchée par l’élévation du taux de glucose dans le sang.Dans une nouvelle étude menée chez la souris, l’équipe dirigée par Alexandre Benani, chercheur CNRS au Centre des Sciences du Goût et de l’Alimentation (2) montre que les circuits de neurones qui freinent la prise alimentaire sont activés après un repas et cette activation implique des mouvements de cellules dans le cerveau.Cette étude a été publiée dans Cell Reports le 3 mars 2020.Lire le communiqué de presse : https://bit.ly/3j…

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…

Method for functional study of mitochondria in rat hypothalamus

1872-678X (Electronic) Journal Article Research Support, Non-U.S. Gov't; Different roles of mitochondria in brain function according to brain area are now clearly emerging. Unfortunately, no technique is yet described to investigate mitochondria function in specific brain area. In this article, we provide a complete description of a procedure to analyze the mitochondrial function in rat brain biopsies. Our two-step method consists in a saponin permeabilization of fresh brain tissues in combination with high-resolution respirometry to acquire the integrated respiratory rate of the biopsy. In the first part, we carefully checked the mitochondria integrity after permeabilization, defined exper…

Hypothalamus-specific deletion of socs3 in adult mice enhances hindbrain sensitivity to endogenous satiety signals via oxytocin signaling

Communication sans actes n° 469 (1 page) ; http://www.neurosciences.asso.fr/V2/colloques/SN11/; Leptin is a major contributor to long-term energy homeostasis, through an intracellular transduction pathway involving activation of Stat3 and its feedback inhibitor Socs3, which limits Stat3 activation. Previous studies have shown that Socs3 haploinsufficiency or socs3 deletion in the whole brain or in selective neuronal populations triggers an increased sensitivity to exogenous leptin, through increased Stat3 activation, and protects against diet-induced obesity in mice fed a high fat diet. Intriguingly however, no phenotype was detected when Socs3 mutant mice were maintained under standard die…

Lack of Hypothalamus Polysialylation Inducibility Correlates With Maladaptive Eating Behaviors and Predisposition to Obesity

This original research article (6 p.) is part of the research topic . Specialty section: This article was submitted to Neuroenergetics, Nutrition and Brain Health, a section of the journal Frontiers in Nutrition.; International audience; High variability exists in individual susceptibility to develop overweight in an obesogenic environment and the biological underpinnings of this heterogeneity are poorly understood. In this brief report, we show in mice that the vulnerability to diet-induced obesity is associated with low level of polysialic acid-neural cell adhesion molecule (PSA-NCAM), a factor of neural plasticity, in the hypothalamus. As we previously shown that reduction of hypothalami…