Descripción del proyecto
La obesidad y la comunicación entre el cerebro y los órganos del aparato digestivo
La comunicación neural entre el cerebro y los órganos del aparato digestivo ayuda a supervisar los órganos gastrointestinales y contribuye a la regulación de la energía y de la homeostasis de la glucosa. Su perturbación produce obesidad y está relacionada con la ingesta excesiva y la resistencia a la insulina. Este proyecto financiado con fondos europeos utilizará una combinación de herramientas de la neurociencia molecular moderna y enfoques genéticos con ratones para determinar la identidad de las neuronas que inervan los órganos del aparato digestivo, definir su papel en los comportamientos alimentarios y el metabolismo de la glucosa, y mapear los neurocircuitos para llegar hasta los puntos específicos en el cerebro. Los resultados satisfactorios del proyecto ayudarán a superar los retos asociados con dirigirse a distintas neuronas de una forma específica según el tipo celular y el órgano, lo que constituye un primer paso importante para desarrollar nuevas terapias para tratar la obesidad.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
80539 Munchen
Alemania