Descrizione del progetto
Come fa il cervello a percepire il glucosio?
Gli alimenti contenenti glucosio hanno un elevato valore di ricompensa per il cervello, poiché il glucosio costituisce la fonte primaria di energia per le cellule. I neuroni e i circuiti del sistema nervoso centrale che percepiscono il glucosio regolano l’omeostasi del glucosio, i processi metabolici, l’assunzione di cibo e il comportamento. Inoltre controllano la funzione degli organi periferici e la secrezione ormonale. Il progetto INTEGRATE, finanziato dal Consiglio europeo della ricerca, si concentra sul ruolo dei neuroni sensibili al glucosio nel comportamento alimentare e sul modo in cui sono deregolati nelle malattie metaboliche. I ricercatori caratterizzeranno la composizione molecolare di queste cellule ed esploreranno il modo in cui l’alimentazione influenza la loro funzione. Nel complesso, il progetto INTEGRATE fornirà importanti informazioni sulla salute metabolica, aprendo la strada a nuovi approcci terapeutici per i disturbi metabolici.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health sciencesbasic medicinephysiologyhomeostasis
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
- medical and health scienceshealth sciencesnutritionobesity
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-ADG - Advanced GrantIstituzione ospitante
1015 LAUSANNE
Svizzera