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Central integration of metabolic and hedonic cues in metabolic health

Description du projet

Comment le cerveau détecte-t-il le glucose?

Les aliments qui contiennent du glucose ont une valeur gratifiante élevée pour le cerveau, dans la mesure où le glucose constitue la principale source d’énergie des cellules. Les neurones et circuits du système nerveux central qui détectent le glucose régulent l’homéostasie du glucose, les processus métaboliques, la consommation alimentaire et le comportement. Ils contrôlent également le fonctionnement des organes périphériques et la sécrétion d’hormones. Financé par le Conseil européen de la recherche, le projet INTEGRATE se consacre au rôle des neurones capteurs de glucose dans le comportement alimentaire et à leur dérégulation dans les maladies métaboliques. Les chercheurs caractériseront la composition moléculaire de ces cellules et étudieront l’influence de la nutrition sur leur fonction. Collectivement, le projet INTEGRATE fournira de précieuses informations sur la santé métabolique, ouvrant la voie à de nouvelles approches thérapeutiques des troubles métaboliques.

Objectif

During evolution the brain has selected glucose as a main source of metabolic energy. This has imposed homeostatic and behavioral constraints. First, the glycemic levels must be maintained at a minimum of ~5 mM to ensure constant energy supply to the brain. Second, a high reward value has to be attributed to glucose-containing foods to increase the motivation to obtain them. These homeostatic and hedonic regulations depend on glucose sensing cells and neuronal circuits in the central nervous system. These cells and circuits regulate the activity of the sympathetic and parasympathetic nerves, which control the function of peripheral organs (liver, fat, muscles) and the secretion of glucagon and insulin by pancreatic islet cells. They also attribute a reward value to glucose-containing foods to control food-seeking behavior, a process that involves the mesolimbic dopaminergic system. Here, we will focus on three interrelated aims:
1. Identify the physiological role of glucose sensing neurons of the ventromedial hypothalamic nucleus (VMN, a key feeding and glucoregulatory center) in glucose homeostasis and food preference; identify their cellular diversity and their molecular make-up; and characterize their deregulations in metabolic diseases.
2. Characterize the molecular physiology of glucose sensing neurons of the paraventricular thalamus, which modulate the activity of the mesolimbic dopaminergic system to control motivated sucrose-seeking behavior; determine their control by other interoceptive signals, including from glucose sensing cells of the VMN.
3. Establish new molecular approaches to characterize, at the molecular and functional levels, the impact of early postnatal nutrition on the development and function of central glucose sensing cells in the control of adult animal physiology.
These studies will open-up new perspectives in the understanding of homeostatic and hedonic regulatory pathways, which preserve metabolic health over a lifetime.

Régime de financement

ERC-ADG - Advanced Grant

Institution d’accueil

UNIVERSITE DE LAUSANNE
Contribution nette de l'UE
€ 2 499 714,00
Adresse
QUARTIER UNIL CENTRE - BATIMENT UNICENTRE
1015 LAUSANNE
Suisse

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Région
Schweiz/Suisse/Svizzera Région lémanique Vaud
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 2 499 714,00

Bénéficiaires (1)