A plastic aggrecan barrier modulated by peripheral energy state gates metabolic signal access to arcuate neurons

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 and Virginie Mattot ()
Additional contact information
Laura Kuczynski-Noyau: UMR-S1172, EGID
Sixtine Karmann: UMR-S1172, EGID
Paolo Alberton: LMU
Ines Martinez-Corral: UMR-S1172, EGID
Sreekala Nampoothiri: UMR-S1172, EGID
Florent Sauvé: UMR-S1172, EGID
Tori Lhomme: UMR-S1172, EGID
Carmelo Quarta: U1215
Suneel S. Apte: Department of Biomedical Engineering
Sébastien Bouret: UMR-S1172, EGID
Attila Aszodi: LMU
Sowmyalakshmi Rasika: UMR-S1172, EGID
Philippe Ciofi: U1215
Julie Dam: Université Paris Cité
Vincent Prévot: UMR-S1172, EGID
Virginie Mattot: UMR-S1172, EGID

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: 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.

Date: 2024
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50798-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50798-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-50798-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().