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

Author

Listed:
  • Manuela Sánchez-Feutrie

    (The Barcelona Institute of Science and Technology
    Universitat de Barcelona
    Universitat de Barcelona
    Instituto de Salud Carlos III)

  • Montserrat Romero

    (The Barcelona Institute of Science and Technology
    Universitat de Barcelona
    Instituto de Salud Carlos III
    Universitat de Barcelona (UB))

  • Sónia R. Veiga

    (The Barcelona Institute of Science and Technology
    Universitat de Barcelona
    Instituto de Salud Carlos III)

  • Núria Borràs-Ferré

    (The Barcelona Institute of Science and Technology
    Universitat de Barcelona
    Instituto de Salud Carlos III
    Universitat de Barcelona (UB))

  • 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
    RadboudUMC)

  • Alba Sabaté-Pérez

    (The Barcelona Institute of Science and Technology
    Universitat de Barcelona
    Instituto de Salud Carlos III
    University Medical Center Rotterdam)

  • Ángela Rodríguez Pérez

    (The Barcelona Institute of Science and Technology)

  • Luis Rodrigo Cataldo

    (The Barcelona Institute of Science and Technology
    Lund University Diabetes Centre
    University of Copenhagen)

  • Hans Burghardt

    (The Barcelona Institute of Science and Technology
    Universitat de Barcelona
    Instituto de Salud Carlos III)

  • David Sebastián

    (The Barcelona Institute of Science and Technology
    Instituto de Salud Carlos III
    University of Barcelona)

  • 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
    Universitat de Barcelona
    Instituto de Salud Carlos III)

  • Remy Burcelin

    (Team INCOMM Rangueil Hospital)

  • Per Antonson

    (Karolinska Institutet)

  • Jan-Ake Gustafsson

    (Karolinska Institutet
    University of Houston)

  • Antonio Zorzano

    (The Barcelona Institute of Science and Technology
    Universitat de Barcelona
    Instituto de Salud Carlos III)

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.

Suggested Citation

  • 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 &, 2025. "Identification of Neuritin 1 as a local metabolic regulator of brown adipose tissue," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62255-2
    DOI: 10.1038/s41467-025-62255-2
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    References listed on IDEAS

    as
    1. Yu-Hua Tseng & Efi Kokkotou & Tim J. Schulz & Tian Lian Huang & Jonathon N. Winnay & Cullen M. Taniguchi & Thien T. Tran & Ryo Suzuki & Daniel O. Espinoza & Yuji Yamamoto & Molly J. Ahrens & Andrew T., 2008. "New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure," Nature, Nature, vol. 454(7207), pages 1000-1004, August.
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    3. Xing Zeng & Mengchen Ye & Jon M. Resch & Mark P. Jedrychowski & Bo Hu & Bradford B. Lowell & David D. Ginty & Bruce M. Spiegelman, 2019. "Innervation of thermogenic adipose tissue via a calsyntenin 3β–S100b axis," Nature, Nature, vol. 569(7755), pages 229-235, May.
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