Short-term impact of a Western diet on the physiology of the peripheral olfactory system

Current feeding behaviors contribute to the epidemic levels of obesity and diabetes observed in Europe and worldwide. Both the quantity and the quality of ingested food are incriminated. Together with other sensory modalities, olfaction is involved in the control of food intake. Olfactory cues can influence eating behaviors, yet the nutritional status and diet can also alter olfactory abilities. Patients with metabolic disorders present impaired olfactory sensitivity which could in turn worsen their eating behaviors.Here we examined the short-term impact of a Western diet enriched in fat and sugar (High Fat High Sugar, HFHS) on the anatomy and physiology of the olfactory epithelium of postn…

O12 Implication de la Cx43 dans la détection hypothalamique du glucose

Introduction L'hypothalamus est fortement implique dans la regulation nerveuse de l'homeostasie glucidique. La detection de l'hyperglycemie par des neurones specialises declenche des reponses adaptees comme le maintien de la glycemie ou encore le rassasiement. Les astrocytes sont suspectes participer a la detection neuronale du glucose. Ils sont organises en reseaux et presentent un grand nombre de jonctions gap (JG) permettant le passage du glucose de la circulation sanguine vers les neurones. Ces JG sont formees majoritairement de connexine 43 (Cx43). Nous avons fait l'hypothese que les reseaux astrocytaires, via les Cx43 en particulier, participent a la detection hypothalamique du glucos…

Implication of Cx43 in hypothalamic detection of glucosis.

Meeting Abstract ; WOS: 000302819400014; International audience

Plasmalogens and cell‐cell communication between retinal glial cells

National audience; Purpose Plasmalogens are glycerophospholipids containing a vinyl‐ether bond at sn‐1 position of their glycerol backbone and polyunsaturated fatty acids (PUFAs) at sn‐2. We have previously shown that plasmalogens are involved in the regulation of perinatal retinal vascular development and particularly in astrocyte template formation (Saab et al, PLoSONE 2012 9(6):e101076). Since retinal Müller cells and astrocytes can communicate through calcium waves and connexin 43‐rich gap junctions, the aim of our study was to determine whether a reduction of plasmalogen levels affects communication between retinal glial cells. Methods Primary Müller cells and astrocyte were isolated f…

P293 Le diabète de type 2 induit un phénotype anxieux irréversible et attenue la réponse aux antidépresseurs chez la souris

Introduction Une alimentation riche en graisse entraine des perturbations metaboliques associees a des troubles psychiatriques. Toutefois, l'impact des traitements antidepresseurs dans la comorbidite diabete/depression reste peu documente. Notre etude vise a comparer les effets d'un inhibiteur selectif de recapture de la serotonine, le escitalopram, sur le comportement anxiodepressif de souris nourries avec un regime hyperlipidique (High-Fat-Diet ou HFD). Materiels et methodes Des souris mâles ont recu un regime standard (STD) ou HFD pendant 16 semaines puis ont ete traitees avec du escitalopram (10mg/kg ; s.c.) ou son solvant (NaCl 0,9 %) pendant les 4 dernieres semaines de regime. Le poid…

O20 Rôle de l’Acyl-CoA Binding Protein dans le contrôle hypothalamique de la balance énergétique

Rationnel Le controle de la balance energetique repose sur la detection de signaux metaboliques incluant les acides gras a longue chaine (AGLC) par l'hypothalamus medio-basal (HMB). Les AGLC agissent dans l'HMB pour inhiber la prise alimentaire et la production de glucose, cependant les voies metaboliques et types cellulaires impliques ne sont pas connus. Acyl-CoA Binding Protein (ACBP) est une proteine intracellulaire liant les AGLC-CoA et controlant leur metabolisme en peripherie. Dans le cerveau, ACBP est connu comme Diazepam Binding Inhibitor, un peptide secrete et clive en octadecaneuropeptide (ODN). L'administration centrale d'ODN exerce une action anxiogene et anorexigene. Cependant,…

The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system

International audience; Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-l…

Dual role of acyl-coa binding protein in the hypothalamus: regulator of astrocyte fatty acid metabolism and gliotransmitter targeting pomc neurons

La liste des auteurs est incomplète.; absent

P185 Canaux TRPC3: nouveau mécanisme impliqué dans la sensibilité hypothalamique au glucose et le contrôle de l’homéostasie énergétique

Introduction L’hypothalamus medio-basal (MBH) renferme des neurones gluco-excites impliques dans le controle de l’homeostasie glucidique. Neanmoins, les mecanismes mis en jeu dans la reponse au glucose de ces neurones sont inconnus mis a part des donnees preliminaires montrant l’implication d’especes actives de l’oxygene (EAOs). Certains canaux de la famille des « transient receptor potential-canonical ° » (TRPC), qui presentent une conductance ionique observee dans les neurones gluco-excites, sont directement modules par les EAOs. Nous avons emis l’hypothese qu’une voie de signalisation EAOs-TRPC-dependante est impliquee dans la reponse au glucose des neurones gluco-excites hypothalamiques…

Membrane potential dye imaging of ventromedial hypothalamus neurons from adult mice to study glucose sensing

Studies of neuronal activity are often performed using neurons from rodents less than 2 months of age due to the technical difficulties associated with increasing connective tissue and decreased neuronal viability that occur with age. Here, we describe a methodology for the dissociation of healthy hypothalamic neurons from adult-aged mice. The ability to study neurons from adult-aged mice allows the use of disease models that manifest at a later age and might be more developmentally accurate for certain studies. Fluorescence imaging of dissociated neurons can be used to study the activity of a population of neurons, as opposed to using electrophysiology to study a single neuron. This is par…

Causal Link between n-3 Polyunsaturated Fatty Acid Deficiency and Motivation Deficits

International audience; Reward-processing impairment is a common symptomatic dimension of several psychiatric disorders. However, whether the underlying pathological mechanisms are common is unknown. Herein, we asked if the decrease in the n-3 polyunsaturated fatty acid (PUFA) lipid species, consistently described in these pathologies, could underlie reward-processing deficits. We show that reduced n-3 PUFA biostatus in mice leads to selective motivational impairments. Electrophysiological recordings revealed increased collateral inhibition of dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) onto dopamine D1 receptor-expressing MSNs in the nucleus accumbens, a main brain regio…

Evidence for hypothalamic ketone bodies sensing: impact on food intake and peripheral metabolic responses in mice

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain keton…

Plasmalogen depletion in Müller glia alters both Cx43 expression and gap junction intercellular communication with neighbouring astrocytes

International audience

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, …

Alteration of hypothalamic glucose sensing in high fat-high sucrose diet fed rats: early defects linked to mitochondrial dynamics and mROS signalling

Involvement of reactive oxygen species and TRP channels in glucose sensitivity of hypothalamic neuron

Involvement of reactive oxygen species in glucose sensitivity of hypothalamic neuron

Impact of type 2 diabetes on depressive-like phenotype and antidepressant response in mice

Abstract at the 17th Annual Meeting of French Society of Pharmacology and Therapeutics, the 80th Annual Meeting of Society of Physiology, the 34th Pharmacovigilance Meeting, the 14th APNET Seminar and the 11th CHU CIC Meeting, 22-24 April 2013, Angers, France.; International audience; Evidence indicates that the prevalence of depression in diabetic subjects is higher than that in the general population. Despite these observations, the mechanisms underpinning the link between metabolic and psychiatric disorders are poorly understood. Moreover, it has been proposed that an impairment of glucose homeostasis may result in blunted antidepressant response to selective serotonin reuptake inhibitor…

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

Hypothalamic Astroglial Connexins are Required for Brain Glucose Sensing-Induced Insulin Secretion

Supplementary Information accompanies the paper on the Journal of Cerebral Blood Flow & Metabolism website; Hypothalamic glucose detection participates in maintaining glycemic balance, food intake, and thermogenesis. Although hypothalamic neurons are the executive cells involved in these responses, there is increasing evidence that astrocytes participate in glucose sensing (GS); however, it is unknown whether astroglial networking is required for glucose sensitivity. Astroglial connexins 30 and 43 (Cx30 and Cx43) form hexameric channels, which are apposed in gap junctions, allowing for the intercellular transfer of small molecules such as glucose throughout the astroglial networks. Here, we…

Defective insulin secretory response to intravenous glucose in C57Bl/6J compared to C57Bl/6N mice

Objective: The C57Bl/6J (Bl/6J) mouse is the most widely used strain in metabolic research. This strain carries a mutation in nicotinamide nucleotide transhydrogenase (Nnt), a mitochondrial enzyme involved in NADPH production, which has been suggested to lead to glucose intolerance and beta-cell dysfunction. However, recent reports comparing Bl/6J to Bl/6N (carrying the wild-type Nnt allele) under normal diet have led to conflicting results using glucose tolerance tests. Thus, we assessed glucose-stimulated insulin secretion (GSIS), insulin sensitivity, clearance and central glucose-induced insulin secretion in Bl/6J and N mice using gold-standard methodologies. Methods: GSIS was measured u…

Glucose excites hypothalamic neurons through the activation of Transient Receptor Potential Canonical (TRPC) channels

International audience

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…

High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice

BACKGROUND AND PURPOSE The link between type 2 diabetes mellitus (T2DM) and depression is bidirectional. However, the possibility that metabolic disorders may elicit anxiogenic-like/depressive-like symptoms or alter the efficacy of antidepressant drugs remains poorly documented. This study explored the influence of T2DM on emotionality and proposed a therapeutic strategy that might be used in depressed diabetic patients. EXPERIMENTAL APPROACH Mice were fed a high-fat diet (HFD) and subjected to a full comprehensive metabolic and behavioural analysis to establish correlations between metabolic and psychiatric disorders. In vivo intra-hippocampal microdialysis was also applied to propose a me…

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…

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 …

Fasting enhances the response of arcuate neuropeptide Y-glucose-inhibited neurons to decreased extracellular glucose

0363-6143 (Print) Comparative Study In Vitro Journal Article Research Support, N.I.H., Extramural; Fasting increases neuropeptide Y (NPY) expression, peptide levels, and the excitability of NPY-expressing neurons in the hypothalamic arcuate (ARC) nucleus. A subpopulation of ARC-NPY neurons ( approximately 40%) are glucose-inhibited (GI)-type glucose-sensing neurons. Hence, they depolarize in response to decreased glucose. Because fasting enhances NPY neurotransmission, we propose that during fasting, GI neurons depolarize in response to smaller decreases in glucose. This increased excitation in response to glucose decreases would increase NPY-GI neuronal excitability and enhance NPY neurotr…

CA-139: Impact précoce d'un régime gras et sucré sur la perception olfactive

Introduction L'odorat est un sens primordial pour guider les choix alimentaires. Certains patients diabetiques presentent une alteration de leurs capacites olfactives. De nombreuses interactions existent entre les hormones impliquees dans la regulation de l'homeostasie energetique et le systeme olfactif. Cependant, les consequences du diabete sur le systeme olfactif sont peu connues. Nous avons ici etudie les effets precoces d'un regime diabetogene enrichi en gras et sucre sur le systeme olfactif de souris. Materiels et Methodes Des souris mâles ont ete alimentees pendant 8 semaines avec un regime diabetogene enrichi en graisse et en sucre (HFHS). L'etat metabolique des animaux a ete caract…

Hypothalamic S-Nitrosylation Contributes to the Counter-Regulatory Response Impairment following Recurrent Hypoglycemia

http://www.ncbi.nlm.nih.gov/pubmed/23894333; International audience; AIMS: Hypoglycemia is a severe side effect of intensive insulin therapy. Recurrent hypoglycemia (RH) impairs the counter-regulatory response (CRR) which restores euglycemia. During hypoglycemia, ventromedial hypothalamus (VMH) production of nitric oxide (NO) and activation of its receptor soluble guanylyl cyclase (sGC) are critical for the CRR. Hypoglycemia also increases brain reactive oxygen species (ROS) production. NO production in the presence of ROS causes protein S-nitrosylation. S-nitrosylation of sGC impairs its function and induces desensitization to NO. We hypothesized that during hypoglycemia, the interaction b…

CA-153: Étude des propriétés de type anxiolytiques/antidépresseurs de la Metformine dans un modèle murin de diabète de type 2

Introduction Le diabete de type 2 (DT2) peut entrainer des symptomes depressifs. La metformine et la fluoxetine peuvent etre prescrits conjointement dans la comorbidite diabete-depression. Le but de cette etude etait donc de determiner les effets respectifs de ces agents pharmacologiques et de leur association sur le controle glycemique et les comportements emotionnels. Ceci a ete realise chez des souris soumises a un regime standard ou hyperlipidique connu pour entrainer des troubles de l'humeur. Materiels et Methodes 80 souris mâles (C57Bl/6 j) ont ete repartis en deux groupes nourris avec un regime standard (STD) ou hyperlipidique (HF : 45 % gras) pendant 16 semaines. A la semaine 13, le…

Impact du diabete de type 2 sur l'etat de type “dépressif” chez la souris

La liste des auteurs est incomplète.; absent

Gap junction intercellular communication (GJIC) is regulated by plasmalogens in retinal macroglial cells

International audience

PO22 Comportements de type anxieux et dépréssif induit par un régime alimentaire hyperlipidique chez la souris adulte

Introduction Des etudes epidemiologiques suggerent que l’anxiete/depression et le diabete de type 2 (DT2) sont etroitement lies. Cependant, peu d’etudes precliniques appuient ce concept, ce qui renforce la necessite de developper un modele animal de la comorbidite entre DT2 et comportement anxio/depressif. Le but de ce projet est de determiner si les troubles metaboliques liees a la consommation d’un regime alimentaire riche en graisse (HF) induit le developpement de comportements de type anxio/depressif. Materiels et methodes Des souris mâles agees de 7 ou 15 semaines ont ete nourris avec un regime standard (STD) ou HF pendant 8 semaines. Le gain de poids, la glycemie a jeun, la tolerance …

Glucose and hypothalamic astrocytes: More than a fueling role?

Brain plays a central role in energy homeostasis continuously integrating numerous peripheral signals such as circulating nutrients, and in particular blood glucose level, a variable that must be highly regulated. Then, the brain orchestrates adaptive responses to modulate food intake and peripheral organs activity in order to achieve the fine tuning of glycemia. More than fifty years ago, the presence of glucose-sensitive neurons was discovered in the hypothalamus, but what makes them specific and identifiable still remains disconnected from their electrophysiological signature. On the other hand, astrocytes represent the major class of macroglial cells and are now recognized to support an…