Identification of Neuritin 1 as a local metabolic regulator of brown adipose tissue

Manuela Sánchez-Feutrie (), Montserrat Romero, Sónia R. Veiga, Núria Borràs-Ferré, Nick Berrow, Martina Ràfols, Noemí Giménez, Andrea Rodgers-Furones, Alba Sabaté-Pérez, Ángela Rodríguez Pérez, Luis Rodrigo Cataldo, Hans Burghardt, David Sebastián, Natàlia Plana, Vanessa Hernández, Laura Isabel Alcaide, Óscar Reina, Maria J. Monte, José Juan G. Marin, Manuel Palacín, Remy Burcelin, Per Antonson, Jan-Ake Gustafsson and Antonio Zorzano ()
Additional contact information
Manuela Sánchez-Feutrie: The Barcelona Institute of Science and Technology
Montserrat Romero: The Barcelona Institute of Science and Technology
Sónia R. Veiga: The Barcelona Institute of Science and Technology
Núria Borràs-Ferré: The Barcelona Institute of Science and Technology
Nick Berrow: The Barcelona Institute of Science and Technology
Martina Ràfols: The Barcelona Institute of Science and Technology
Noemí Giménez: The Barcelona Institute of Science and Technology
Andrea Rodgers-Furones: The Barcelona Institute of Science and Technology
Alba Sabaté-Pérez: The Barcelona Institute of Science and Technology
Ángela Rodríguez Pérez: The Barcelona Institute of Science and Technology
Luis Rodrigo Cataldo: The Barcelona Institute of Science and Technology
Hans Burghardt: The Barcelona Institute of Science and Technology
David Sebastián: The Barcelona Institute of Science and Technology
Natàlia Plana: The Barcelona Institute of Science and Technology
Vanessa Hernández: The Barcelona Institute of Science and Technology
Laura Isabel Alcaide: The Barcelona Institute of Science and Technology
Óscar Reina: The Barcelona Institute of Science and Technology
Maria J. Monte: ISCIII
José Juan G. Marin: ISCIII
Manuel Palacín: The Barcelona Institute of Science and Technology
Remy Burcelin: Team INCOMM Rangueil Hospital
Per Antonson: Karolinska Institutet
Jan-Ake Gustafsson: Karolinska Institutet
Antonio Zorzano: The Barcelona Institute of Science and Technology

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Brown adipose tissue (BAT) plays a key role in metabolic homeostasis through its thermogenic effects and the secretion of regulatory molecules. Here we report that RAP250 haploinsufficiency stimulates BAT in mice, thus contributing to a decrease in fat accumulation. Local in vivo AAV-mediated RAP250 silencing in BAT reduces body weight and fat mass and enhances glucose oxidation, thereby indicating that RAP250 participates in the regulation of BAT metabolic activity. Analysis of the mechanisms led to the finding that Neuritin 1 is produced and released by brown adipocytes, it plays a key metabolic role, and it participates in the enhanced BAT metabolic activity under RAP250 deficiency. Forced overexpression of Neuritin 1 in UCP1-expressing cells markedly decreases fat mass and body weight gain in mice and induces the expression of thermogenic genes in BAT. Neuritin 1-deficient brown adipocytes also shows a reduced β-adrenergic response. We demonstrate a metabolic role of BAT-derived Neuritin 1 acting through an autocrine/paracrine mechanism. Based on our results, Neuritin-1 emerges as a potential target for the treatment of metabolic disorders.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62255-2 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:16:y:2025:i:1:d:10.1038_s41467-025-62255-2

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

DOI: 10.1038/s41467-025-62255-2

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 ().