Descripción del proyecto
Obesidad infantil y desarrollo neuronal
La obesidad representa una carga en todo el mundo y la obesidad infantil está reconocida como un importante problema de salud. El proyecto financiado con fondos europeos ONTOGENY tiene por objeto descubrir los procesos del desarrollo importantes para controlar la homeostasis energética. Las neuronas hipotalámicas que expresan péptido relacionado con la proteína agouti (AgRP, por sus siglas en inglés) pueden estimular la ingesta de alimentos, mientras que las neuronas que expresan proopiomelanocortina (POMC) inhiben el comportamiento alimentario. El proyecto estudiará la ontogenia tardía de las neuronas que expresan AgRP y POMC midiendo su actividad durante el desarrollo del ratón en respuesta a los nutrientes y las hormonas implicados en la homeostasis energética. En última instancia, ofrecerá información importante sobre el desarrollo de las neuronas que expresan AgRP y POMC en condiciones pertinentes para la desregulación metabólica y la obesidad infantil.
Objetivo
Obesity is a significant global burden that is associated with adverse health outcomes. Adults are not alone in their struggles with obesity. Children now accumulate fat at an alarming rate, making childhood obesity a major health problem. Unfortunately, we do not know enough about the pathophysiology of these conditions to propose appropriate prevention strategies and more effective therapeutic approaches. In this ERC StG proposal, our goal is to discover the developmental processes important for proper con-trol of energy homeostasis. We will study Agrp and POMC neurons, located in the arcuate nucleus of the hypothalamus, that are heavily involved with control of energy homeostasis. Agrp and POMC neu-rons have delayed postnatal development, maturing their axonal projections around the third postnatal week in rodents. Here, we will study in detail this late ontogeny of Agrp and POMC neurons. In Aim 1, we will use novel approaches to measure Agrp and POMC neuronal activity during mouse development in response to nutrients and hormones involved in energy homeostasis. In Aim 2, we will use whole-brain imaging techniques to determine the anatomical development of Agrp and POMC neuronal projec-tions. We will also study the importance of a specific neuronal circuit in neonates to the development of obesity. Finally, in Aim 3, we will identify critical molecular mechanisms involved in the ontogeny of Agrp and POMC neurons by investigating their translatome over the course of postnatal development. Overall, this project will provide novel insights into Agrp and POMC neuron development in conditions relevant to childhood obesity and metabolic dysregulation. The functional, anatomical and molecular mechanisms illuminated here will provide the foundation for future studies aimed to dissect the devel-opment of other homeostatic systems.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
OX1 2JD Oxford
Reino Unido