The physio-pathological relevance of an unexplored “lateral diffusion barrier” separating the metabolic brain from the bloodstream – MetaboGate

Control of energy homeostasis requires a permanent dialogue between the periphery and the brain. The median eminence (ME) is at the interface between the bloodstream and the hypothalamic arcuate nucleus (ARH), a key center controlling metabolism. Blood-borne molecules reach the ME parenchyma but cannot diffuse into the ARH due to the lateral diffusion barrier (LDB) which nature and plasticity are completely unknown. Data suggest that tissue biophysical properties at the LDB account for molecule blockage in this region. This project will explore the contribution of these biophysical properties in the establishment of the LDB, in its physiological plasticity to regulate energy homeostasis and in its impairment during metabolic disorders. Hence, the role played by the extracellular matrix and a specific molecule involved in tissue resiliency will be explored using atomic force microscopy, MALDI imaging, in vivo models and molecular approaches to decipher the physio-pathological relevance of the LDB.