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5th Symposium Nutrition & Neuroscience, CNRS UMR 5287 & University of BordeauxOrganiser: Angelo Contarino

Abstract :


Des études ont mis en évidence le lien étroit entre l'alimentation, le bon fonctionnement du cerveau et l'équilibre émotionnel. Nos capacités cognitives, nos performances intellectuelles, notre mémorisation, ainsi que nos capacités d'apprentissage dépendent de nombreuses substances comme les sucres, les vitamines et minéraux, des acides aminés, des acides gras etc. De bonnes raisons pour la tenue de ce cinquième Symposium "Alimentation et Neuroscience" organisé par Angelo Contarino. L'occasion pour ces 11 scientifiques de présenter leurs derniers travaux. Symposium ouvert à tous (en anglais), pas d'inscription ! voir le programme détaillé...

 

11h15-11h30

Angelo Contarino
Welcome and presentation of sessions


         
11h30-12h00

Authors: Chloe Boitard & Guillaume Ferreira

Affiliation: NutriNeuro, INRA UMR 1286, University of Bordeaux.

Title: Modulation of memory and plasticity by early high-fat diet consumption: bidirectional effects on hippocampus and amygdala

Abstract: Consumption of high-fat diet (HFD) is a major cause of the current obesity pandemic. In humans, obesity leads to adverse cognitive and emotional outcomes. The growing population of young obese is of a major concern since hippocampal and amygdala maturation during childhood and adolescence may determine adult cognitive and emotional functions. We thus evaluated in rodents the consequences of 2-3 months of HFD consumption immediately after weaning (i.e. covering adolescence) on hippocampal-dependent and amygdala-dependent memory and plasticity. Early HFD consumption impaired hippocampal-dependent memory (spatial memory in rats and relational memory in mice) whereas it enhanced amygdala-dependent emotional memory (assessed either through conditioned odor aversion or cued fear conditionning). Interestingly, the effects on spatial and aversive memory were specific to long term memory, suggesting an effect of early HFD on consolidation processes and not on acquisition. Moreover, HFD consumption restricted to adulthood was without consequences on either spatial, relational or aversive memory. We then evaluated whether HFD-induced memory alterations could be related to synaptic plasticity changes. We simultaneously assessed long-term potentiation (LTP) in the pathways from entorhinal cortex to basolateral amygdala and hippocampal CA1 in anaesthetized rats. Early HFD consumption (2-3 months) enhanced LTP in both hippocampus and amygdala whereas longer HFD consumption (5-6 months) enhanced LTP in amygdala but impaired LTP in hippocampus. Taken together, these results suggest a bidirectional modulation of hippocampal and amygdala functions by early HFD consumption, at both the behavioral and synaptic levels.

           
         
12h00-12h30

Authors: Thomas Larrieu & Sophie Layé

Affiliation: NutriNeuro, INRA UMR 1286, University of Bordeaux.

Title: Anxiety-like symptoms induced by n-3 polyunsaturated fatty acids dietary deficiency: what are the mechanisms?

Abstract: Low intake of essential n-3 polyunsaturated fatty acids (PUFAs) has been paralleled with depression in western countries as documented in epidemiological studies. This was recently highlighted in our previous study in mice demonstrating that one generation of imbalance in the ratio of n-6:n-3 PUFAs induces synaptic plasticity alteration in the prefrontal cortex (PFC) accompanied by a depressive/anxiety-like behaviors. However, the pathways through which the consumption of imbalanced n-3 PUFAs diet leads to mood alterations are still unclear. Studies using chronic stress as a model of depression/anxiety in rodents have unveiled neuronal dendritic remodeling in PFC induced by corticosterone elevation. Here, we first examined the effect of long term n-3 deficient diet on dendritic morphology of pyramidal neurons within the PFC, corticosterone level as well as depressive/anxiety-like behaviors. We show that n-3 deficient diet induces dendritic atrophy in the PFC correlated with the intensity of emotional alterations and corticosterone elevation. Interestingly, mice fed with a balanced n-3 diet and submitted to social defeat stress showed the same neurological and behavioral alterations than the one described in nonstressed n-3 deficient mice. No additional effect of chronic social stress on both neuronal morphology and behaviors was measured in n-3 deficient mice. Phenotype similarities between n-3 deprivation and chronic social stress prompted us to further investigate the role of the hypothalamic-pituitary-adrenal (HPA) axis in the development of behavioral and neurobiological troubles of n-3 deficient mice. In addition, we further studied whether a diet enriched in n-3 PUFAs is able to ameliorate neurological and behavioral impairment induced by n-3 PUFAs dietary deficiency. All together, our results show that low dietary n-3 PUFAs, without any exposure to stressful events induces emotional behaviors impairment, neuronal dendritic alterations and involve HPA axis activation.
           
           
         
12h30-13h00

Authors: Edgar Soria-Gomez & Giovanni Marsicano

Affiliation: INSERM, Neurocentre Magendie, Bordeaux, France

Title: Cannabinoid type-1 (CB1)-dependent regulation of food intake in the olfactory bulb

Abstract: Cannabinoid receptor type-1 (CB1)-dependent signaling in the brain exerts a bimodal control of stimulated food intake, by differentially regulating excitatory and inhibitory synaptic transmission. However, the brain sites where this complex control is exerted are not fully understood yet. Here, using anatomical behavioural and electrophysiological approaches, we identified the olfactory bulb (OB) as one of the brain sites involved in the hyperphagic effects of cannabinoids. By using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) we characterized the CB1 receptors in the olfactory bulb. At mRNA level, CB1 is present in glomeruli and in the mitral cell layer. Importantly, we found that CB1 protein is mainly expressed in centrifugal glutamatergic feedbacks (coming from the olfactory cortex) in the granular cell layer. We show that CB1 antagonism or enhancing glutamatergic transmission in the OB blocks the hyperphagic effect of systemic Δ9-tetrahydrocannabinol (THC, an agonist of CB1 receptors). Furthermore, NMDA antagonism in the OB is able to revert the documented hypophagic phenotype of GLU-CB1-KO mice, lacking CB1 receptors in cortical glutamatergic neurons (Bellocchio et al., 2010). Recordings of local field potentials in the OB of anesthetized mice, revealed that hyperphagic doses of THC prevent odor habituation, i.e the decrease of beta oscillatory activity in response to multiple odorant stimulations. Hence, CB1 activation in the OB regulates food intake through modifications of glutamatergic transmission and odor habituation.

           
          BUFFET
           
         
15h00-15h30

Authors: Elke Binder & Daniela Cota

Affiliation: Group “Energy Balance and Obesity”, INSERM U862, University of Bordeaux.

Title: Metabolic effects of leucine supplementation on the prevention of diet-induced obesity

Abstract: Previous investigations have suggested that chronic supplementation with the amino acid leucine might protect against the development of diet-induced obesity (DIO) and its associated metabolic dysregulation. However, the evidence available so far is equivocal and insufficient.
In the current study we investigated whether the chronic supplementation of leucine (LEU) in drinking water could protect mice from the development of DIO. We observed that HFD-LEU mice gained significantly less weight and fat mass, compared to HFD-water controls, while no changes in food intake were observed. Leucine supplementation during HFD significantly increased energy expenditure and improved insulin sensitivity. Gut gluconeogenesis, as assessed by the activity of the G6pase enzyme, was increased in HFD-LEU as compared to HFD-water mice. Leucine supplementation also led to improved glucose-stimulated insulin secretion in Langerhans islets.
Finally, molecular analysis suggests that leucine supplementation during HFD prevents gene expression modifications induced by HFD consumption and might therefore impede molecular changes favoring metabolic dysregulation and obesity.

Supported by: Ajinomoto Amino Acid Research Programme; Marie Curie Intra-European Post-doctoral fellowship FP7-People2009-IEF-251494; INSERM

           
           
         
15h30-16h00

Author: Jose Luis Santos

Affiliation: Department of Nutrition, Diabetes and Metabolism, Pontificia Universidad Católica de Chile, Santiago, Chile

Title: Identification of the genetic cause of severe hypertriglyceridemia through homozygosity mapping

Abstract: Severe hypertriglyceridemia (HTG) has been linked to genetic defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes, with possible involvement of unidentified mutations in additional genes. Very high triglyceride plasma levels (>10,000 mg/dL at diagnosis) were found in two sisters from a Chilean consanguineous family, with a genetic pattern strongly suggestive of a highly penetrant recessive mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG present in this consanguineous family. We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNPs in the proband and her affected sister, with no excess of homozygosity in unaffected relatives. The 11q genomic region includes the APOA5/A4/C3/A1 cluster with contains strong candidate genes for severe HTG. Direct sequencing of the APOA5 gene revealed a homozygous Q97X mutation (c.289C>T) present in both affected sisters but not in non-affected relatives or in a sample of unrelated controls. Therefore, the Q97X mutation of the APOA5 gene in homozygosity status is responsible for the severe HTG in this family. Homozygosity mapping combined with exome sequencing is expected to be a very potent strategy in the identification of genetic causes of monogenic diseases.

          

16h00-16h30

Author: Pedro Prieto-Hontoria

Affiliation: Dept. of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, Pamplona

Title: Lipoic acid as a fascinating therapeutic agent for obesity and inflammation

Abstract: Our group investigates the effects of dietary supplementation with lipoic acid (LA) on body weight gain, adiposity, and insulin sensitivity in control and high fat fed rats. The changes induced by LA on several adipokines involved in the regulation of body weight and glucose homeostasis such as leptin, adiponectin and chemerin were also tested both in vivo and in different models of cultured adipocytes.
LA supplementation induced a lower body weight gain and adipose tissue size in rats accompanied by a reduction in food intake. Moreover, LA reduced feed efficiency and decreased intestinal α-methylglucoside absorption. LA treatment also improves insulin sensitivity, which was accompanied by an upregulation of adiponectin gene expression in white adipose tissue. The in vitro studies revealed that LA inhibited chemerin secretion and mRNA levels in both 3T3-L1 adipocytes and in subcutaneous and omental adipocytes from obese subjects. Moreover, LA was able to abolish the stimulatory effects of the pro-inflammatory cytokine TNF-α on chemerin secretion. In summary, these findings suggest that LA could be a potential therapeutic agent for the treatment of some of the metabolic complications associated to obesity.

Keywords: Lipoic Acid, Obesity, Adipose Tissue, Adipokines

          

16h30-17h00

Author: Pedro González-Muniesa

Affiliation: Dept. of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, Pamplona Title: Oxygen therapy and Weight management Abstract: Oxygen is indispensable for cell metabolism, and in turn, an adequate tissue oxygenation is essential for all normal physiological functions in most living creatures. Therefore, diseases as important nowadays as cancer, obesity or respiratory dysfunctions are known to be related with a poor tissue oxygenation.
Back in 2004, Trayhurn and Wood, published a hypothesis about hypoxia and inflammation within adipose tissue, suggesting that the expanded adipose tissue of obese people suffers a poor oxygenation that affects adipokines production and triggers the inflammatory cascade. Since then, several research groups from different parts of the world have confirmed their hypothesis.
Interestingly, environmental hypoxic conditions (like high altitudes) have been related to reduced appetite, weight loss and fine cardiovascular health in fit subjects. Thus hypoxic conditions could be used to ameliorate the obesity status and improved cardiovascular parameters on obese subjects. On the other hand, hyperoxia is commonly used to treat diseases developed due to poor oxygenation. Therefore, a high concentration of oxygen could be selected as a therapy to inhibit the inflammatory cascade occurring within hypoxic adipose tissue. The knowledge gathered from these two hypotheses will be very helpful to generate an oxygen therapy protocol able to counteract obesity and its pernicious symptoms as a whole, or at least part of these symptoms.