Taste disorders in disease

Among the different sensory systems, gustation is one of the most elaborate. In its sensory task, gustation is helped by interactions with other sensory systems (olfaction, vision, audition, and somatosensory, trigeminal and thermal sensations). It allows the detection and identification of soluble compounds which can be ingested or must be avoided. This function is fundamental to ingestive behavior (energy intake and selection of nutrients) in order to meet physiological needs. Taste is also fundamental to the genesis of hedonic sensations and, therefore, the desire to eat (appetite). The tasting step is also the first stage of the digestion, absorption, and storage of nutrients due to ant…

The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms.

Objectives:\ud The corticotrophin-releasing factor (CRF)/urocortin system is expressed in the adipose tissue of mammals, but its functional role in this tissue remains unknown.\ud \ud Methods:\ud Pharmacological manipulation of the activity of CRF receptors, CRF1 and CRF2, was performed in 3T3L1 white pre-adipocytes and T37i brown pre-adipocytes during in vitro differentiation. The expression of genes of the CRF/urocortin system and of markers of white and brown adipocytes was evaluated along with mitochondrial biogenesis and cellular oxygen consumption. Metabolic evaluation of corticosterone-deficient or supplemented Crhr1-null (Crhr1−/−) mice and their wild-type controls was performed alo…

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…

Preconditioning by Mitochondrial Reactive Oxygen Species Improves the Proangiogenic Potential of Adipose-Derived Cells-Based Therapy

Objective— Transplantation of adipose-derived stroma cells (ADSCs) stimulates neovascularization after experimental ischemic injury. ADSC proangiogenic potential is likely mediated by their ability to differentiate into endothelial cells and produce a wide array of angiogenic and antiapoptotic factors. Mitochondrial reactive oxygen species (ROS) have been shown to control ADSC differentiation. We therefore hypothesized that mitochondrial ROS production may change the ADSC proangiogenic properties. Methods and Results— The use of pharmacological strategies (mitochondrial inhibitors, antimycin, and rotenone, with or without antioxidants) allowed us to specifically and precisely modulate mito…

Evaluation of whole antioxidant defenses of human mononuclear cells by a new in vitro biological test: lack of correlation between erythrocyte and mononuclear cell resistance to oxidative stress

1873-2933 (Electronic) Journal Article; OBJECTIVES: This work aims to evaluate the resistance of mononuclear cells to oxidative stress using a "KRL" test, formerly utilized to evaluate the resistance of erythrocyte to free radicals. METHODS: The "KRL" test evaluates the resistance to lysis of cells treated by free radicals generated under standardized conditions. RESULTS: We defined new analytical parameters (level of radical production, time course, number of cells) to obtain an accurate assay determining the resistance to oxidative stress of mononuclear cells, in comparison to that of erythrocytes. This test allows the evaluation of change in the redox state of mononuclear cells (improved…

Perception périphérique des signaux sensoriels. 1- Gustation

National audience

Implication of Cx43 in hypothalamic detection of glucosis.

Meeting Abstract ; WOS: 000302819400014; International audience

Chatting Between the Brain and White Adipose Tissues

Over the past decades, numerous papers have been published demonstrating the importance of the relationships between the brain and white adipose tissues in regard to body weight and metabolism regulation. Indeed the brain mainly via the sympathetic nervous system control body fat mass both by regulating adipocytes metabolism (lipolysis and lipogenesis), secretory activity (leptin and other adipokines) as well as development. In turn fat mass will send information to some brain areas via sensory nerves as well as via changes in metabolic and hormonal signals. Altogether these data are in support of a feedback loop between white adipose tissues and the brain. This crosstalk plays a major role…

Potentiels évoqués gustatifs chez l’homme en réponse à une stimulation sucrée

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…

Contrôle du métabolisme intermédiaire par les systèmes nerveux central et périphérique

La regulation du metabolisme intermediaire resulte de la mise en jeu de deux mecanismes, ľun hormonal, ľautre nerveux. Ces deux systemes interagissent de maniere coordonnee. En ce qui concerne le mecanisme nerveux, le systeme nerveux autonome joue un role primordial, en particulier en modulant directement le metabolisme au niveau de certains organes (foie, muscles, tissus adipeux) et en regulant indirectement la secretion de differentes hormones, principalement les hormones pancreatiques mais egalement ľactivite endocrine des tissus adipeux.

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,…

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…

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…

[Hedonic perception and taste of food in patients with type 2 diabetes - Impact of treatment with a GLP-1: Liraglutide] / P19 Perception hédonique et gustative des aliments chez les patients diabétiques de type 2 - Impact du traitement par un analogue du GLP-1 : le Liraglutide

Special Issue 2 : Résumés des communications de la réunion scientifique de la SFD, de la SFD Paramédical et de l'AJD ; WOS: 000302819400145; International audience

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…

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…

Impact des rythmes circadiens sur l'exocytose des granules d'insuline

Impact des rythmes circadiens sur l'exocytose des granules d'insuline. congrès de la société francophone du Diabète (SFD)

Spatial reconstruction of Drosophila NPF neurons

Spatial reconstruction of Drosophila NPF neurons. SENC XIV

Modification des ingestions protéiques par la séance d’hémodialyse : une piste pour lutter contre la dénutrition

Introduction La denutrition proteino-energetique est un facteur de risque de mortalite chez les patients (P) en hemodialyse (HD). Le but de l’etude est de determiner si les apports alimentaires sont modifies par la seance d’HD et d’en rechercher d’eventuels mediateurs. Patients et methodes Un large choix d’aliments est propose a des P dialyses, non diabetiques, non fumeurs, sans comorbidite evolutive, 2 jours consecutifs a 12 heures apres l’HD et un jour sans HD. Les P choisissent la nature et la quantite d’aliments et leurs ingestions sont quantifiees. Des questionnaires avec echelle visuelle analogique permettent d’evaluer les criteres de choix des aliments. Les concentrations plasmatique…

Mechanisms involved in the control of feeding behavior in relation to food flavor

Revue; IntroductionIntake is one of the most essential behaviors, since human beings, like any living organism, require adequate nutrients for their survival. Ingestive behavior is controlled to maintain energy balance by peripheral and central mechanisms. When physiological needs are not being met, they will lead to motivation. Thus, being hungry will motivate us to find food, and the motivation will cease when needs are met. Ingestive behavior is thus initially due to a need related to internal signals (Fig. 10.1), in this case, hunger (physiological need) and appetite (urge to eat a food from which we expect pleasure and satisfaction). Sensory (visual, olfactory and, to a lesser extent, …

Mitochondrial reactive oxygen species are obligatory signals for glucose-induced insulin secretion.

OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. Here, we investigate whether transient mitochondrial ROS production linked to glucose-induced increased respiration might act as a signal for monitoring insulin secretion. RESEARCH DESIGN AND METHODS—ROS production in response to glucose was investigated in freshly isolated rat islets. ROS effects were studied using a pharmacological approach and calcium imaging. RESULTS—Transient glucose increase …

Bases physiologiques de la satiété et de la digestion

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

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…

Le goût : physiologie, rôles et dysfonctionnements

Article de vulgarisation; National audience; The sense of taste involves multimodal sensory activation to detect and identify many flavors. Today, five primary tastes have been identified (sweet, salt, sour, bitter and umami). These are often combined to form complex tastes. The physiology of gustatory pathways is complex. The activation of gustatory receptors located in the mouth leads to an ascendant pathway through the neurons of the solitary nucleus in the brainstem and the neurons located in the thalamus. After the thalamus, the gustative signal modulates the ipsilateral primary taste cortex and then the secondary taste area. The secondary taste cortex, which combines representations o…

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…

PO20 Impact des rythmes circadiens sur l’exocytose des granules d’insuline

Introduction La cellule β possede une horloge circadienne autonome regulee par les genes « horloge ». Parmi ces genes, les recepteurs nucleaires Rev-erbα et β repriment le facteur de transcription Bmal1, au cœur de l’horloge. Ces genes « horloge » couplent les rythmes circadiens au metabolisme glucidique. Rev-erbα est implique dans la secretion d’insuline en reponse au glucose en regulant notamment des genes de la machinerie d’exocytose. Une desynchronisation de l’horloge est a l’origine d’une secretion d’insuline inadaptee. Pour mieux comprendre ce mecanisme, nous avons etudie l’impact de l’horloge circadienne sur les etapes distales de l’exocytose par la cellule β. Materiels et methodes L…

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 …

Leptin and the central control of feeding behavior.

International audience; The discovery of leptin by Friedman and coll. in 1995 was a major step forward in our comprehensive view of energy homeostasis. Since the original paper, a tremendous amount of work has been performed in laboratories all over the world. Many recent reviews have described this work in details. In the present review, we focus on the role of leptin on food intake. It is accepted by most authors working in this field that the control of food intake can be divided in two closely-related system: the homeostatic system and the hedonic system. Leptin has been shown to act on both systems.

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…

Adipose tissue lymphocytes: types and roles

Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except …

Role of the basolateral amygdala in retrieval of conditioned flavors in the awake rat.

International audience; Learned association between odor, taste and further post-ingestive consequence is known as flavor nutrient conditioned preference. Amygdala is supposed to be one of the areas involved in these associations. In the present study, one flavor was associated with a 16% glucose (CS+) whereas another flavor was paired with less reinforcing 4% glucose (CS-). We showed that CS+ presentation after conditioning increased Fos expression in the basolateral nucleus of amygdala (BLA). Furthermore, we performed electrophysiological recordings in the BLA in free moving rats. After preference acquisition, rats were exposed to either the CS+ or the CS-. The proportion of neurons showi…

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…

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…

Sensory-specific satiety for a food is unaffected by the ad libitum intake of other foods during a meal. Is SSS subject to dishabituation?

Sensory-specific satiety (SSS) is defined as a decrease in the pleasantness of a specific food that has just been eaten to satiation, while other non-eaten foods remain pleasant. The objectives of this study were the following: (1) to investigate whether SSS for a food is affected by the ad libitum intake of other foods presented sequentially during a meal, (2) to compare the development of SSS when foods are presented simultaneously or sequentially during a meal, and (3) to examine whether SSS is modified when foods are presented in an unusual order within a meal. Twelve participants participated in three tasting sessions. In session A, SSS for protein-, fat- and carbohydrate-rich sandwich…

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…

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

P217: Potentiels evoqués gustatifs chez l’Homme en réponse à une stimulation sucrée

Introduction et but de l’etude Les Potentiels Evoques Gustatifs (PEG) peuvent etre detectes en reponse a une stimulation intermittente des recepteurs gustatifs par une saveur primaire. Ils permettent d’explorer la voie sensorielle gustative depuis les bourgeons du gout jusqu’au cortex gustatif. Notre objectif etait double : (1) etablir un enregistrement fiable des PEG chez l’Homme, et (2) determiner les variations physiologiques de l’activite evoquee electrique cerebrale en regard des aires gustatives en fonction de l’intensite du stimulus puis en fonction de l’etat de jeune ou de satiete. Materiel et methodes Des sujets volontaires sains ont ete inclus. Lors d’une 1 re experience, une solu…

Gustatory evoked cortical activity in humans in response to saccharin stimuli

National audience; Introduction/Objectives: Gustatory Evoked Potentials (GEP) can be detected in response to an intermittent stimulation of the gustatory receptors by a primary flavour. Contrary the other evoked cortical potentials (visual, auditory or sensory), GEP have not been extensively studied due to their recording heterogeneity. Our aim was to establish a reliable recording of GEP in Humans. Methods: Voluntary and healthy subjects were included in this experiment. A saccharin solution with several concentrations (5, 10 or 20g per 100mL) was used as the gustatory stimulus. Each session was performed on a different day, with an interval of at least 2 hours after eating or drinking. Co…

Sensory functions and Alzheimer's disease: a multi-disciplinary approach

Relations between sensory functions and Alzheimer's disease are still under-explored. To understand them better, the Fondation Médéric Alzheimer has brought together a multi-disciplinary expert group. Aristote's five senses must be enhanced by today's knowledge of proprioception, motor cognition and pain perception. When cognition breaks down, the person with dementia perceives the world around her with her sensory experience, yet is unable to integrate all this information to understand the context. The treatment of multiple sensory inputs by the brain is closely linked to cognitive processes. Sensory deficits reduce considerably the autonomy of people with dementia in their daily life and…

Taste of Fat and Obesity: Different Hypotheses and Our Point of View

Obesity results from a temporary or prolonged positive energy balance due to an alteration in the homeostatic feedback of energy balance. Food, with its discriminative and hedonic qualities, is a key element of reward-based energy intake. An alteration in the brain reward system for highly palatable energy-rich foods, comprised of fat and carbohydrates, could be one of the main factors involved in the development of obesity by increasing the attractiveness and consumption of fat-rich foods. This would induce, in turn, a decrease in the taste of fat. A better understanding of the altered reward system in obesity may open the door to a new era for the diagnosis, management and treatment of th…

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

Organisateur de la conférence : Fondation Mérieux ; http://www.fondation-merieux.org/Food-for-better-health; International 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…

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…

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…

Influence of substrate oxidation ratio on food intake, food wanting and food consumption in humans

National audience

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.

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…

Hedonic perception and taste of food in patients with type 2 diabetes - Impact of treatment with a GLP-1: Liraglutide.

potentiels évoqués gustatifs chez l'Homme en réponse à une stimulation sucrée

International audience

Potentiels évoqués gustatifs chez l'Homme en réponse à une stimulation sucrée

National audience

Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 deficiency reduces leukocyte infiltration into adipose tissue and favors fat deposition

1525-2191 (Electronic) Journal Article; Obesity is associated with low-grade inflammation and leukocyte infiltration in white adipose tissue (WAT) and is linked to diabetic complications. Semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1 (SSAO/VAP-1), is a membrane protein that is highly expressed in adipocytes and is also present on the endothelial cell surface where it is involved in leukocyte extravasation. We studied fat deposition and leukocyte infiltration in WAT of mice with a null mutation in the amine oxidase copper-containing-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-month-old AOC3-KO males than in age-matc…

Alteration of hypothalamic glucose and lactate sensing in 48h hyperglycemic rats.

International audience; Hypothalamic detection of nutrients is involved in the control of energy metabolism and is altered in metabolic disorders. Although hypothalamic detection of blood lactate lowers hepatic glucose production and food intake, it is unknown whether it also modulates insulin secretion. To address this, a lactate injection via the right carotid artery (cephalad) was performed in Wistar rats. This triggered a transient increase in insulin secretion. Rats made hyperglycemic for 48h exhibited prolonged insulin secretion in response to a glucose injection via the carotid artery, but lactate injection induced two types of responses: half of the HG rats showed no difference comp…

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 …

Influence substrate oxidation ratio on food liking, food wanting and food consumption in humans

Meeting Abstract; International audience; Influence substrate oxidation ratio on food liking, food wanting and food consumption in humans

La privation de sommeil fait grossir : mythe ou réalité ?

Resume Notre rythme de vie actuel a entraine une diminution progressive du temps alloue au sommeil. En France, une personne sur 3 dormirait moins de 7 heures par nuit. Dans le meme temps, le nombre de patients souffrant d’obesite a augmente. De nombreuses etudes epidemiologiques soulignent le lien entre la faible duree du temps de sommeil et la prise de poids. En parallele, les etudes experimentales ont observe que la privation de sommeil modifiait le comportement alimentaire en augmentant la sensation de faim et la prise alimentaire. Le cycle nycthemeral induit par l’alternance lumiere–obscurite a une influence majeure sur le sommeil mais aussi sur le comportement alimentaire : la lumiere …

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…

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…

Relationships between adipose tissues and brain: what do we learn from animal studies?

International audience; Over the last decades, more and more data supporting the importance of the relationships between the brain and adipose tissues (white and brown) in regards of body weight regulation and energy homeostasis have been published. Indeed the brain via the autonomic nervous system participates to the regulation of different parameters such as the metabolic (lipolysis, lipogenesis and thermogeneis), and secretory (leptin and other adipokines) activities but also plasticity (proliferation differentiation and apoptosis) of adipose tissues. In turn the various fat pads will send information via sensory innervation of white adipose tissue as well as metabolic and hormonal signa…

032 Implication de la Cx43 dans le glucose-sensing hypothalamique

Introduction L’hypothalamus est fortement implique dans la regulation de l’homeostasie glucidique. Les variations de glycemie y sont detectees par des neurones specialises, notamment dans le noyau arque : on parle de « glucose-sensing » (GS). L’integration de cette information declenche une reponse adaptee afin de maintenir la glycemie stable. L’acheminement du glucose de la circulation aux neurones implique les astrocytes. Ces derniers forment un reseau via les jonctions gap (JG) qui permet le trafic de metabolites, dont le glucose, entre astrocytes et avec le milieu extracellulaire. Ces jonctions sont formees majoritairement de connexines 43 (Cx43), hemi-canaux fortement exprimes dans l’h…

Haemodialysis in patients with chronic renal failure increases the wanting for foods rich in proteins

Haemodialysis in patients with chronic renal failure increases the wanting for foods rich in proteins. 24. Annual Meeting of the European-Chemoreception-Research-Organization (ECRO)

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…

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…

Gustatory evoked cortical activity in humans in response to saccharose stimuli

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 …

Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells

Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. As adipose tissues were recently demonstrated to contain pluripotent stem cells, the emergence of cardiomyocyte phenotype from adipose-derived cells was investigated. We demonstrated that rare beating cells with cardiomyocyte features could be identified after culture of adipose stroma cells without addition of 5-azacytidine. The cardiomyocyte phenotype was first identified by morphological observation, confirmed with expression of specific cardiac markers, immunocy…

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…

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…

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…

Influence of respiratory quotient on food liking, food wanting, macronutrients selection and food consumption

International audience

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…

Influence du liraglutide (analogue du GLP-1) sur les caractéristiques hédoniques de la prise alimentaire et les performances gustatives, chez les patients diabétiques de type 2

Titre anglais : Treatment by GLP-1 agonist modulates hedonic responses to food and taste sensitivity in obese type 2 diabetes mellitus patients

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…

COVID 19-Induced Smell and Taste Impairments: Putative Impact on Physiology

This article is part of the Research Topic "The Tribute of Physiology for the Understanding of COVID-19 Disease".; International audience; Smell and taste impairments are recognized as common symptoms in COVID 19 patients even in an asymptomatic phase. Indeed, depending on the country, in up to 85-90% of cases anosmia and dysgeusia are reported. We will review briefly the main mechanisms involved in the physiology of olfaction and taste focusing on receptors and transduction as well as the main neuroanatomical pathways. Then we will examine the current evidences, even if still fragmented and unsystematic, explaining the disturbances and mode of action of the virus at the level of the nasal …

Adipose tissue sensitivity to radiation exposure

1525-2191 (Electronic) Journal Article Research Support, Non-U.S. Gov't; Treatment of cancer using radiation can be significantly compromised by the development of severe acute and late damage to normal tissue. Treatments that either reduce the risk and severity of damage or that facilitate the healing of radiation injuries are being developed, including autologous adipose tissue grafts to repair tissue defects or involutional disorders that result from tumor resection. Adipose tissue is specialized in energy storage and contains different cell types, including preadipocytes, which could be used for autologous transplantation. It has long been considered a poorly proliferative connective ti…