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Symposium - Meeting Nutrition & Neurosciences 2013

Abstract :

Organisateurs:  Sophie Layé, Véronique Pallet, Catherine Suberville, NutriNeuro, Bordeaux

Program

9h45 Welcome

10h-10h30 Edgar Soria "Activation of the sympathetic nervous system mediates hypophagic and anxiety-related effects of CB1 receptor blockade",  Neurocentre Magendie, Bordeaux

10h30-11h Coffee break

11h-11h30 Marie-Pierre Moisan “Differential body weight regulation  after high fat diet and chronic stress: analysis of the  transcortin-deficient mouse”,  NutriNeuro, Bordeaux

11h30-12h Martine Cador, Hedonic vs motivational properties of food in rodents INCIA, Bordeaux

12h-12h30  Charlotte Madore, Effects of n-3 deficiency on brain innate immune system,  NutriNeuro, Bordeaux

12h45  Lunch

14h30-15h  Pierre Cardinal, “Diet-dependent role of VMN CB1 cannabinoid receptor signaling in the regulation of energy balance”, Neurocentre Magendie, Bordeaux

15h-15h30 Amelia Marti del Moral “The problem of childhood obesity”, Dpt of Nutrition, Food Science and Physiology, School of Pharmacy, University of Navarra, Spain

15h30 -16h Break

16h-16h30 Bruno Aouizerate "A new method for the characterization of pleasure for food in obesity and relationships with the endocannabinoid system", Neurocentre Magendie, Bordeaux

16h30-17h Fermin Milagro “Chronobiology and obesity: recent insights”, Dpt of Nutrition, Food Science and Physiology, School of Pharmacy, University of Navarra, Spain


Abstracts

A.M. Minni, E. Cadon, J.C. Helbling, S. Layé, V. Pallet, N. Castanon and M.P. Moisan.
Differential body weight regulation after high fat diet and chronic stress: analysis of the transcortin-deficient mouse

Adequate regulation of energy and food intake under stress is important for survival. The hypothalamic-pituitary-adrenal (HPA) axis is not only the ‘conductor’ of an appropriate stress response, but is also tightly intertwined with the endocrine regulation of appetite and energy metabolism. We have recently created a mouse model with a targeted deletion of transcortin also called corticosteroid binding globulin (CBG). We found that this mouse model has a dysregulated hypothalamo-pituitary-adrenal (HPA) axis impacting on behavioral and endocrine stress responses. Recently, we have observed that submitting these mice to a Western lifestyle characterized by high fat diet and chronic stress lead to modulation of weight regulation that differ to what happen to wild-type mice under the same treatments. The transcortin-deficient mice gain weight under high-fat diet like the wild-type mice but present a dramatic weight loss when chronic stress is combined while wild-type mice preserve their weight under the same conditions. Detailed analysis of the metabolic responses of the transcortin-deficient mice points out to an increased lipolysis as the main factor explaining the differential weight regulation. Thus, this study highlights the importance of the HPA axis in energy metabolism under Western life-style.

Edgar Soria and Giovanni Marsicano,
"Activation of the sympathetic nervous system mediates hypophagic and anxiety-related effects of CB1 receptor blockade", Neurocentre Magendie 

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the site(s) where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal (GI) metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the GI tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii (NTS) abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptors blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.

Pierre Cardinal and Daniela Cota,
“Diet-dependent role of VMN CB1 cannabinoid receptor signaling in the regulation of energy balance”, Neurocentre Magendie 

The endocannabinoid system (ECS) plays a key role in energy balance regulation but its functions within discrete hypothalamic nuclei known to regulate energy balance have not been established. The hypothalamic ventromedial nucleus (VMN) regulates food intake and energy expenditure. Although cannabinoid type 1 receptor (CB1) signaling is involved in these two mechanisms, a complete understanding of its role within the VMN is still missing. To answer this question, we deleted CB1 gene in SF1 neurons of the VMN, and evaluated the impact of this deletion on energy balance regulation in mice. VMN-CB1-KO mice were characterized by an approximately 80% decrease in CB1 mRNA levels in the VMN. Under standard diet and compared to their wild-type (WT) littermates, VMN-CB1-KO mice displayed a significant decrease in fat mass, better glucose tolerance and increased sensitivity to leptin and insulin. This was associated with a decreased respiratory quotient and increased mRNA levels of the β3-adrenergic receptor in the white adipose tissue. Conversely, when exposed to a high-fat diet, VMN-CB1-KO mice had increased food intake, body weight and fat mass as compared to WT, together with decreased hypothalamic leptin receptor mRNA expression. These results suggest that CB1 signaling in the VMN differently affects energy balance according to the diet consumed, a phenomenon that might involve interaction between CB1 and leptin receptor signaling in the VMN.


AMELIA MARTI, Pharm D, PhD. Professor of Physiology. Department of Nutrition, Food Science, Physiology, University of Navarra, Pamplona, Spain.  
GENE VARIANTS AND OBESITY: THE EVASYON STUDY

Advances in genetics, such as sequencing of the human genome, have contributed to identification of susceptible genetic patterns in complex diseases such as obesity. The revolution started in 2006 thanks to the widespread availability of genome arrays and the subsequent proliferation of genome wide association studies (GWAS). These efforts have resulted in the identification of about 40 loci related to human obesity. Of those, FTO has been the most replicated and the one showing the highest statistical significance. However, despite these advances, the combined effect of all loci identified so far account for about 2-3% of the inherited contribution to obesity risk (40-70%). These humbling statistics confirm the complex nature of obesity and the need to identify additional factors including interactions between multiple genes and environmental factors. Here I will present some examples of the influence of obesity-related gene variants in the response to a nutritional intervention the EVASYON study (a weight loss program for Spanish obese adolescents).

 

Fermin I. Milagro, Department of Nutrition, Food Science and Physiology, University of Navarra
Chronobiology and obesity: recent insights

Among the putative causal factors contributing to excessive fat accumulation, sleep duration and quality, meal times and epigenetics have been recently proposed. For example, patients with visceral obesity exhibit disturbances in the circadian rhythm (chronodisruption) that may be associated with higher weight increase and development of diabetes and atherosclerotic disease, whereas prolonged short sleep durations could increase appetite, compromise insulin sensitivity and raise blood pressure. It has been demonstrated that different factors related to shiftwork (that is related to obesity risk), such as job seniority, length of shiftwork, and morning and evening types, are associated with the DNA methylation of the promoters of glucocorticoid receptor, TNF-α and IFN-γ genes in peripheral blood cells. Circadian rhythm is regulated by different clock genes, including CLOCK, PER2 or BMAL1. In this context, SNPs in PER2 and CLOCK have been related with caloric intake, circulating cytokine and ghrelin levels, eating behaviour and attrition in weight-loss treatments. Moreover, long-term shiftwork induces hypomethylation in the promoter of CLOCK gene and hypermethylation of CRY2 in peripheral blood DNA. These data suggest that a relationship between clock gene dysregulation and obesity and MetS may exist. We have found that epigenetic mechanisms involving clock genes (i.e., methylation status of CpG sites located in clock genes) may be useful in obesity prevention and the success of weight reduction programs. Of note, our data pave the way to the study of epigenetic mechanisms in the regulation of circadian rhythms in relation to obesity and weight loss.

Catherine Noël Suberville (catherine.noel-suberville @ u-bordeaux1.fr)