| Autor: |
Laura Kuczynski-Noyau, Sixtine Karmann, Paolo Alberton, Ines Martinez-Corral, Sreekala Nampoothiri, Florent Sauvé, Tori Lhomme, Carmelo Quarta, Suneel S. Apte, Sébastien Bouret, Attila Aszodi, Sowmyalakshmi Rasika, Philippe Ciofi, Julie Dam, Vincent Prévot, Virginie Mattot |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-11 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-50798-9 |
| Popis: |
Abstract The hypothalamic arcuate nucleus (ARH) contains neurons vital for maintaining energy homeostasis that sense and respond to changes in blood-borne metabolic hormones. Despite its juxtaposition to the median eminence (ME), a circumventricular organ lacking a blood-brain barrier and thus exposed to circulating molecules, only a few ventral ARH neurons perceive these extravasating metabolic signals due to a poorly understood ME/ARH diffusion barrier. Here, we show in male mice that aggrecan, a perineural-net proteoglycan deposited by orexigenic ARH neurons, creates a peculiar ventrodorsal diffusion gradient. Fasting enhances aggrecan deposition more dorsally, reinforcing the diffusion barrier, particularly around neurons adjacent to fenestrated capillary loops that enter the ARH. The disruption of aggrecan deposits results in unregulated diffusion of blood-borne molecules into the ARH and impairs food intake. Our findings reveal the molecular nature and plasticity of the ME/ARH diffusion barrier, and indicate its physiological role in hypothalamic metabolic hormone sensing. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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