Feeding Our Immune System: Impact on Metabolism

Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose) impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs) of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy

Interleukin-7, a New Cytokine Targeting the Mouse Hypothalamic Arcuate Nucleus: Role in Body Weight and Food Intake Regulation

Body weight is controlled through peripheral (white adipose tissue) and central (mainly hypothalamus) mechanisms. We have recently obtained evidence that overexpression of interleukin (IL)-7, a critical cytokine involved in lymphopoiesis, can protect against the development of diet-induced obesity in mice. Here we assessed whether IL-7 mediated its effects by modulating hypothalamic function. Acute subcutaneous injection of IL-7 prevented monosodium glutamate-induced obesity, this being correlated with partial protection against cell death in the hypothalamic arcuate nucleus (ARC). Moreover, we showed that IL-7 activated hypothalamic areas involved in regulation of feeding behavior, as indicated by induction of the activation marker c-Fos in neural cells located in the ventromedial part of the ARC and by inhibition of food intake after fasting. Both chains of the IL-7 receptor (IL-7Rα and γc) were expressed in the ARC and IL-7 injection induced STAT-3 phosphorylation in this area. Finally, we established that IL-7 modulated the expression of neuropeptides that tune food intake, with a stimulatory effect on the expression of pro-opiomelanocortin and an inhibitory effect on agouti-related peptide expression in accordance with IL-7 promoting anorectic effects. These results suggest that the immunomodulatory cytokine IL-7 plays an important and unappreciated role in hypothalamic body weight regulation

Ghrelin Gene Deletion Alters Pulsatile Growth Hormone Secretion in Adult Female Mice

Using preproghrelin-deficient mice (Ghrl-/-), we previously observed that preproghrelin modulates pulsatile growth hormone (GH) secretion in post-pubertal male mice. However, the role of ghrelin and its derived peptides in the regulation of growth parameters or feeding in females is unknown. We measured pulsatile GH secretion, growth, metabolic parameters and feeding behavior in adult Ghrl-/- and Ghrl+/+ male and female mice. We also assessed GH release from pituitary explants and hypothalamic growth hormonereleasing hormone (GHRH) expression and immunoreactivity. Body weight and body fat mass, linear growth, spontaneous food intake and food intake following a 48-h fast, GH pituitary contents and GH release from pituitary explants ex vivo, fasting glucose and glucose tolerance were not different among adult Ghrl-/- and Ghrl+/+ male or female mice. In vivo, pulsatile GH secretion was decreased, while approximate entropy, that quantified orderliness of secretion, was increased in adult Ghrl-/- females only, defining more irregular GH pattern. The number of neurons immunoreactive for GHRH visualized in the hypothalamic arcuate nucleus was increased in adult Ghrl-/- females, as compared to Ghrl+/+ females, whereas the expression of GHRH was not different amongst groups. Thus, these results point to sex-specific effects of preproghrelin gene deletion on pulsatile GH secretion, but not feeding, growth or metabolic parameters, in adult mice.Fil: Hassouna, Rim. Université Paris Cité; Francia. Universite de Bordeaux; Francia. Inserm; FranciaFil: Fernandez, Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Lebrun, Nicolas. Université Paris Cité; FranciaFil: Fiquet, Oriane. Universite de Bordeaux; Francia. Université Paris Cité; Francia. Inserm; FranciaFil: Roelfsema, Ferdinand. Leiden University Medical Center; Países BajosFil: Labarthe, Alexandra. Université Paris Cité; Francia. Universite de Bordeaux; Francia. Inserm; FranciaFil: Zizzari, Philippe. Universite de Bordeaux; Francia. Université Paris Cité; Francia. Inserm; FranciaFil: Tomasetto, Catherine. Universite de Bordeaux; Francia. Université Paris Cité; Francia. Inserm; FranciaFil: Epelbaum, Jacques. Universite de Bordeaux; Francia. Université Paris Cité; Francia. Inserm; FranciaFil: Viltart, Odile. Universite de Bordeaux; Francia. Université Paris Cité; Francia. Inserm; FranciaFil: Chauveau, Christophe. Université Du Littoral Côte D‘opale; FranciaFil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Tolle, Virginie. Université Paris Cité; Franci

Changes in CRH and ACTH Synthesis during Experimental and Human Septic Shock

Context The mechanisms of septic shock-associated adrenal insufficiency remain unclear. This study aimed at investigating the synthesis of corticotropin-releasing hormone (CRH) and vasopressin (AVP) by parvocellular neurons and the antehypophyseal expression of ACTH in human septic shock and in an experimental model of sepsis. Objective To test the hypothesis that ACTH secretion is decreased secondarily to alteration of CRH or AVP synthesis, we undertook a neuropathological study of the antehypophyseal system in patients who had died from septic shock and rats with experimental faecal peritonitis. Methods Brains obtained in 9 septic shock patients were compared to 10 nonseptic patients (controls). Parvocellular expression of AVP and CRH mRNA were evaluated by in situ hybridization. Antehypophyseal expression of ACTH, vasopressin V1b and CRH R1 receptors and parvocellular expression of iNOS in the PVN were evaluated by immunohistochemistry. The same experiments were carried out in a fecal peritonitis-induced model of sepsis. Data from septic rats with (n = 6) or without (n = 10) early death were compared to sham-operated (n = 8) animals. Results In patients and rats, septic shock was associated with a decreased expression of ACTH, unchanged expression of V1B receptor, CRHR1 and AVP mRNA, and increased expression of parvocellular iNOS compared to controls. Septic shock was also characterized by an increased expression of CRH mRNA in rats but not in patients, who notably had a greater duration of septic shock. Conclusion The present study suggests that in humans and in rats, septic shock is associated with decreased ACTH synthesis that is not compensated by its two natural secretagogues, AVP and CRH. One underlying mechanism might be increased expression of iNOS in hypothalamic parvocellular neurons

How valuable are your customers in the brand value co-creation process? The development of a Customer Co-Creation Value (CCCV) scale.

Despite an increasing amount of research on co-creation of value, in general, research on brand value co-creation remains limited. Particularly, how much value customers contribute to the brand value co-creation process remains unclear. This research develops in a series of eight studies the Customer Co-Creation Value (CCCV) measurement scale that helps firms assess the value of customers in the brand value co-creation process. The findings reveal that CCCV is a multidimensional construct consisting of two higher-order factors and seven dimensions: customer-owned resources (including brand knowledge, brand skills, brand creativity, and brand connectedness) and customer motivation (comprising brand passion, brand trust, and brand commitment). Further, the CCCV scale reliably and validly gauges the value customers contribute to a firm's brand. The CCCV framework helps marketing managers understand how customers can contribute to a firm's brand value cocreation efforts and how much value customers contribute to a brand in the co-creation process

Overexpression of Wild-Type Human Alpha-Synuclein Causes Metabolism Abnormalities in Thy1-aSYN Transgenic Mice

Parkinson’s disease is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, pathological accumulation of alpha-synuclein and motor symptoms, but also by non-motor symptoms. Metabolic abnormalities including body weight loss have been reported in patients and could precede by several years the emergence of classical motor manifestations. However, our understanding of the pathophysiological mechanisms underlying body weight loss in PD is limited. The present study investigated the links between alpha-synuclein accumulation and energy metabolism in transgenic mice overexpressing Human wild-type (WT) alpha-synuclein under the Thy1 promoter (Thy1-aSYN mice). Results showed that Thy1-aSYN mice gained less body weight throughout life than WT mice, with significant difference observed from 3 months of age. Body composition analysis of 6-month-old transgenic animals showed that body mass loss was due to lower adiposity. Thy1-aSYN mice displayed lower food consumption, increased spontaneous activity, as well as a reduced energy expenditure compared to control mice. While no significant change in glucose or insulin responses were observed, Thy1-aSYN mice had significantly lower plasmatic levels of insulin and leptin than control animals. Moreover, the pathological accumulation of alpha-synuclein in the hypothalamus of 6-month-old Thy1-aSYN mice was associated with a down-regulation of the phosphorylated active form of the signal transducer and activator of transcription 3 (STAT3) and of Rictor (the mTORC2 signaling pathway), known to couple hormonal signals with the maintenance of metabolic and energy homeostasis. Collectively, our results suggest that (i) metabolic alterations are an important phenotype of alpha-synuclein overexpression in mice and that (ii) impaired STAT3 activation and mTORC2 levels in the hypothalamus may underlie the disruption of feeding regulation and energy metabolism in Thy1-aSYN mice

Du rassasiement à la satiété, la place du plaisir sensoriel

National audienceFrom satiation to satiety, the place of sensory pleasure. In a context of increasing obesity, there is an urgent need to understand precisely how the balance between body weight and energy expenditure is managed. To ensure our survival, subtle and sophisticated physiological mechanisms have been developed, including appetite control. Within this framework, sen- sory pleasure, satiation and satiety are key elements in the processes of regulating food intakeDans un contexte d’augmentation croissante de l’obésité, il devient urgent de comprendre de manière précise comment est géré l’équilibre entre le poids corporel et la dépense éner- gétique. Pour assurer notre survie, des mécanismes physiologiques subtils et sophisti- qués ont été développés, incluant le contrôle de l’appétit. Dans ce cadre, le plaisir sensoriel, le rassasiement et la satiété constituent des éléments clés des processus de régulation de la prise alimentaire

Editorial: Eating Disorders From Binge to Anorexia: Basic and Clinical Approaches for a Translational Research.

International audienc

Prenatal stress alter the brain plasticity in adult male rat

Un organisme doit être capable de produire des réponses comportementales, neuroendocrines et neurobiologiques adaptées aux perturbations de son environnement afin de maintenir son homéostasie. La production de ces réponses, appelée allostasie, est permise par des phénomènes de plasticité neuro-comportementale. Le stress prénatal (SP) chez le rat modifie les capacités d'aptation aux perturbations environnementales en induisant, chez l'adulte, une plus grande anxiété, une hyperactivité de l'axe corticotrope, des perturbations des rythmes circadiens... Ces modifications sont-elles associées à des perturbations de la plasticité cérébrale? Nous avons montré que le SP induisait une diminution de la plasticité de l'activation neuronale de certaines structures limbique associé à une diminution du rétrocontrôle négatif de l'axe corticotrope et à une diminution de l'adaptation comportementale lors d'exposition à des situations anxiogènes. Par ailleurs, une diminution de la nneurogénèse et de l'activité des récepteurs métabotropiques au glutamate du gropue I, et une augmentation d'expression du BDNF ont été observées au niveau de l'hippocampe des rats SP mâles uniquement. Ces différents paramètres sont restaurés par un traitement chronique à l'agomélatine, un nouveau type d'antidépresseur ciblant les systèmes mélatoninergiques. Ces effets du SP résulteraient d'altérations de la barrière foeto placentaire. Les altérations de la palsticité cérébrale associées aux diminutions de la plasticité comportementale montrent que le SP induit chez le rat mâle adulte un état puis une surcharge allostatique, pouvant être à l'origine des différentes désadaptations observées chez ces rats.LILLE1-BU (590092102) / SudocSudocFranceF

Caractérisation d'un modèle animal d'anxiété congénitale (étude comportementale, neuroendocrinienne, neurochimique et neuroanatomique)

Les troubles anxieux constituent un problème majeur de santé publique. Une meilleure compréhension de la neurobiologie de l'anxiété s'avère donc nécessaire. Nous avons cherché ainsi à caractériser un modèle animal d'anxiété : des rats présentant respectivement un comportement anxieux fortement et faiblement marqué (HAB, High Anxiety-related-Behaviour; LAB Low Anxiety-related-Behaviour). Sur le plan comportement, nous confirmons que les rats HAB et LAB peuvent être considérés comme un modèle fiable et robuste d'anxiété. Sur le plan endocrinien, les rats HAB se distinguent par une hyperréactivité de l'axe corticotrope associée à une hyporéactivité du système sympathique. Concernant la réactivité cérébrale, les rats HAB se différencient des rats LAB par une activation neuronale différentielle et par une perturbation des systèmes monoaminergiques classiquement impliqués dans cette pathologie. Notre travail apporte donc des arguments significatifs validant ce modèle animal d'anxiété.Les troubles anxieux constituent un problème majeur de santé publique. Une meilleure compréhension de la neurobiologie de l'anxiété s'avère donc nécessaire. Nous avons cherché ainsi à caractériser un modèle animal d'anxiété : des rats présentant respectivement un comportement anxieux fortement et faiblement marqué (HAB, High Anxiety-related-Behaviour; LAB Low Anxiety-related-Behaviour). Sur le plan comportement, nous confirmons que les rats HAB et LAB peuvent être considérés comme un modèle fiable et robuste d'anxiété. Sur le plan endocrinien, les rats HAB se distinguent par une hyperréactivité de l'axe corticotrope associée à une hyporéactivité du système sympathique. Concernant la réactivité cérébrale, les rats HAB se différencient des rats LAB par une activation neuronale différentielle et par une perturbation des systèmes monoaminergiques classiquement impliqués dans cette pathologie. Notre travail apporte donc des arguments significatifs validant ce modèle animal d'anxiété.LILLE1-BU (590092102) / SudocSudocFranceF