Description du projet
Communication intestinale et obésité
La communication neurale intestin-cerveau aide à surveiller les organes gastro-intestinaux et contribue à réguler l’homéostasie de l’énergie et du glucose. Sa perturbation se développe avec l’obésité et est corrélée à la suralimentation et la résistance à l’insuline. Ce projet, financé par l’UE, combinera des outils modernes de neurosciences moléculaires et des approches génétiques de la souris pour déterminer quels neurones innervent l’intestin, définir leur rôle dans le comportement alimentaire et le métabolisme du glucose, et cartographier les circuits neuronaux vers les sites cérébraux en aval. Les résultats positifs du projet contribueront à surmonter les défis associés au ciblage de neurones distincts de manière cellulaire et spécifique aux organes, une première étape importante pour développer de nouvelles thérapies pour traiter l’obésité.
Objectif
Communication between the gut and the brain is essential for metabolic function. Sensory afferent neurons are key gut-brain connectors that monitor gastrointestinal (GI) tract organs, including the stomach, the duodenum, the liver, and the portal vein area, and thereby critically contribute to systemic energy and glucose homeostasis regulation. Disruption of this neural gut-brain communication develops in obesity and correlates with overeating, body weight gain, and insulin resistance. However, the relevant sensory neuronal populations innervating the GI tract organs along with the pertaining underlying metabolic neurocircuitry still remain to be elucidated. To date, advances in this field have been impeded by the challenges associated with targeting distinct sensory neurons of vagal and spinal origin in a cell-type and organ-specific manner, thereby making the accurate determination of their metabolic function highly difficult. Thus, the proposed comprehensive research program will employ a combinatorial set of modern molecular systems neuroscience tools and novel mouse genetic approaches to (1) elucidate the role of specific sensory neurons in feeding behavior and glucose metabolism, (2) determine the functional metabolic neurocircuitry of GI tract-innervating vagal and spinal afferents in an organ-specific manner, (3) study the effects of obesity on their transcriptomes, and (4) map their functional connectivity as well as synaptic adaptions to downstream brain sites. Collectively, the overarching goals of these four autonomous but complementary projects are to gain greater insights into the integral components of sensory neurons as gut-brain connectors in controlling metabolism as a first step to developing new therapies to treat obesity.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
80539 Munchen
Allemagne