H2020Индивидуална стипендия2017–2019

ARC-NeuroHet · Unravelling neuronal heterogeneity in energy homeostasis regulation

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2017-04-01 → 2019-03-31
Финансиране от ЕС: 171 461 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Невронните групи в хипоталамуса на мишките регулират баланса между приема на храна и разхода на енергия. Разбирането на тези процеси помага при борбата с затлъстяването и свързаните с него заболявания като диабет и сърдечно-съдови проблеми.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Unravelling neuronal heterogeneity in energy homeostasis regulation

Obesity is one of the greatest public health challenges worldwide. In the European Union, its prevalence has been steadily increased during the last four decades. It causes a wide range of physical disabilities and psychological problems and drastically increases a person’s risk of developing a number of noncommunicable diseases (NCDs), including cardiovascular disease, cancer and diabetes. Obesity results from the deregulation of energy homeostasis, and recent research using experimental rodent models has expanded our understanding of energy balance regulation. Global energy balance in the organism is controlled by the central nervous system (CNS), which monitors the energy availability and regulates food intake, energy expenditure and substrate use by the peripheral organs. Neurons in the Arcuate nucleus of the hypothalamus (ARC) constantly monitor the energy levels of the organism through sensing metabolic (glucose, fatty acids, etc.) and hormonal (insulin, leptin, etc.) cues carried in the blood. ARC neuronal populations integrate this information and coordinate global metabolism through the regulation of activity of downstream neurons. Inside the ARC, AgRP and POMC neurons have opposing effects on the regulation of energy homeostasis. Moreover, both populations have a high degree of heterogeneity, being composed by several neuronal subpopulations that react to different and specific stimuli. We require brand new experimental approaches to investigate in detail those subpopulations and how they affect the regulation of energy balance. The newly available Dre/rox recombinase technology offer great opportunity to combine with existing technologies (optogenetics, DREADDS, etc.) to produce improved transgenic mouse models. Novel approaches in the design of murine mouse models are indispensable to study with further detail how certain neuronal subpopulations affect energy balance. Additionally, new druggable targets can be discover trough cell sequencing techniques. The knowledge obtained from these studies will help to the scientific and medical community to understand the complex regulation of energy homeostasis, and the possible causes for its deregulation that results in obesity. In the long term, this knowledge will be the basis for new health policies aimed to curb the obesity epidemic.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

This MSCA Reintegration proposal is aimed to study the heterogeneity of neuronal populations implicated in the maintenance of energy balance. Because of their location, neurons in the arcuate nucleus of the hypothalamus (ARC) integrate nutrient and hormonal signals carried in the blood. Then, they regulate downstream neuron’s activity in order to adapt food intake and energy expenditure. Deregulation of energy homeostasis can lead to obesity and diabetes, two of the major chronic diseases in the EU. AgRP neurons, an ARC population, have a prominent role in the regulation of food intake and systemic insulin sensitivity. They establish axonal projections with several brain areas and recent evidences show that each sub-circuit can have a specific function in the regulation of food intake and/or glucose homeostasis. For this fellowship I propose to use an innovative experimental approach to investigate a specific novel AgRP neuronal subpopulation, characterized by the expression of the UDP-receptor, P2Y6, as a first step to unravel the heterogeneity of the total population. Although P2Y6 activation increases short-term food intake, its effects on glucose homeostasis are still unknown. I plan to combine new recombinase technologies with state of the art techniques to genetically identify the AgRP, P2Y6 subpopulation and then: 1) characterize their in vivo dynamic response to physiological activators; 2) map specific AgRP+, P2Y6+ sub-circuits and dissect their role in each facet of energy homeostasis; and 3) investigate new molecular markers, as possible drugable targets. Results from this project will unveil new aspects of neuronal heterogeneity that participate in the regulation of energy homeostasis and will contribute to design new strategies to curb the actual obesity trends. The completion of this MSCA fellowship represents an exceptional opportunity to reinforce my professional maturity and to develop my independent research line.

Оригинален текст от CORDIS (на английски).

Участници

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV · MUNCHENКоординаторГермания