Glial Regulation of Appetite and Satiety Processes
Description: The GRASP consortium has accumulated a series of data showing novel neuroglial processes in the brain of mouse, which that are nutritionally regulated. These processes are activated at the time scale of a meal, and control food intake and metabolism in an adaptive manner to maintain energy homeostasis. Remarkably, these processes place microglial cells and their phagocytic activity and immune function at the core of the brain regulation of feeding behavior. In addition, the GRASP consortium has demonstrated that many brain diseases share chronic activation of the inflammasome in microglia, with ambivalent effects on neuronal function and brain homeostasis. These complementary knowledges support an original concept in which altered microglial signaling in the inflammatory sick brain could be the biological explanation for the associated maladaptive eating behaviors. The GRASP project aims to reveal new biological mechanisms revisiting several dogmas. First, contrary to current view, we want to show an unexpected beneficial function of microglia at the time scale of a meal that promotes satiety in a macronutrient-dependent manner. Second, we want to evidence that microglia use an inflammatory signaling, not to disseminate neurotoxic effects, but to alert the brain promptly and activate an anorectic response to limit over-eating during dietary fat intake. Third, we want to show that microglia can rapidly engulf myelin sheath of the oligodendrocytes not to degrade the brain but to regulate the access of circulating metabolic cues into the brain parenchyma where sensors are present, to finally adjust food intake. Finally, we want to deconstruct all the biological steps of this brain functioning including microglial sensing, microglia-oligodendrocyte crosstalk, microglia-neuron communication and activation of associated neuronal feeding circuits. For translational purpose, we will seek these processes noninvasively in both rodent and human brains. Finally, we want to explore the pathophysiological relevance of this new regulatory pathway during aging, maladaptive eating disorders, and neuroinflammatory diseases, in both preclinical models and human patients. This ground-breaking research is based on innovative experimental models, development of new approaches, and use of cutting-edge technics. Finally, a specific combination of knowledge and skills will be leveraged by the GRASP consortium to reach objectives and reveal new knowledge on food intake regulation during normal and pathological states, focusing on a largely unexplored cell system in this context, namely the brain microglia.
Funder: Agence Nationale de la Recherche
Amount: €35,980
Funding type: grant
Funder scheme: MRSEI
Start date: 2025-06-01
Investigator: Alexandre BENANI
Institution: CENTRE DES SCIENCES DU GOUT ET DE L'ALIMENTATION - UMR 6265 - UMR A1324 - uB 80
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: ANR-25-MRS1-0039
OpenAlex ID: G1073433941