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

Sánchez-Feutrie, Manuela ; Romero, Montserrat ; Veiga, Sónia R. ; Borràs-Ferré, Núria ; Berrow, Nick ; Ràfols, Martina ; Giménez, Noemí ; Rodgers-Furones, Andrea ; Sabaté-Pérez, Alba and Rodríguez Pérez, Ángela , et al. (2025) In Nature Communications 16(1).
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
16
issue
1
article number
7033
publisher
Nature Publishing Group
external identifiers
  • scopus:105015097251
  • pmid:40908286
ISSN
2041-1723
DOI
10.1038/s41467-025-62255-2
language
English
LU publication?
yes
id
b7e9f106-c783-48da-9f8b-c5660129a0aa
date added to LUP
2025-10-02 14:34:46
date last changed
2025-10-09 12:17:40
@article{b7e9f106-c783-48da-9f8b-c5660129a0aa,
  abstract     = {{<p>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.</p>}},
  author       = {{Sánchez-Feutrie, Manuela and Romero, Montserrat and Veiga, Sónia R. and Borràs-Ferré, Núria and Berrow, Nick and Ràfols, Martina and Giménez, Noemí and Rodgers-Furones, Andrea and Sabaté-Pérez, Alba and Rodríguez Pérez, Ángela and Cataldo, Luis Rodrigo and Burghardt, Hans and Sebastián, David and Plana, Natàlia and Hernández, Vanessa and Alcaide, Laura Isabel and Reina, Óscar and Monte, Maria J. and Marin, José Juan G. and Palacín, Manuel and Burcelin, Remy and Antonson, Per and Gustafsson, Jan Ake and Zorzano, Antonio}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Identification of Neuritin 1 as a local metabolic regulator of brown adipose tissue}},
  url          = {{http://dx.doi.org/10.1038/s41467-025-62255-2}},
  doi          = {{10.1038/s41467-025-62255-2}},
  volume       = {{16}},
  year         = {{2025}},
}