IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-15055-9.html
   My bibliography  Save this article

FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis

Author

Listed:
  • Farnaz Shamsi

    (Harvard Medical School)

  • Ruidan Xue

    (Harvard Medical School
    Fudan University)

  • Tian Lian Huang

    (Harvard Medical School)

  • Morten Lundh

    (Harvard Medical School
    University of Copenhagen)

  • Yang Liu

    (New York University School of Medicine)

  • Luiz O. Leiria

    (Harvard Medical School
    University of São Paulo
    University of São Paulo)

  • Matthew D. Lynes

    (Harvard Medical School)

  • Elena Kempf

    (Harvard Medical School
    University of Leipzig)

  • Chih-Hao Wang

    (Harvard Medical School)

  • Satoru Sugimoto

    (Harvard Medical School)

  • Pasquale Nigro

    (Harvard Medical School)

  • Kathrin Landgraf

    (University of Leipzig)

  • Tim Schulz

    (Harvard Medical School
    German Institute of Human Nutrition)

  • Yiming Li

    (Fudan University)

  • Brice Emanuelli

    (University of Copenhagen)

  • Srinivas Kothakota

    (Five Prime Therapeutics)

  • Lewis T. Williams

    (Five Prime Therapeutics)

  • Niels Jessen

    (Aarhus University Hospital
    Aarhus University)

  • Steen Bønløkke Pedersen

    (Aarhus University Hospital
    Aarhus University)

  • Yvonne Böttcher

    (University of Oslo
    Akershus Universitetssykehus
    University of Leipzig)

  • Matthias Blüher

    (University of Leipzig)

  • Antje Körner

    (University of Leipzig)

  • Laurie J. Goodyear

    (Harvard Medical School)

  • Moosa Mohammadi

    (New York University School of Medicine)

  • C. Ronald Kahn

    (Harvard Medical School)

  • Yu-Hua Tseng

    (Harvard Medical School
    Harvard University)

Abstract

Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue (BAT). Using high-throughput library screening of secreted peptides, we identify two fibroblast growth factors (FGF), FGF6 and FGF9, as potent inducers of UCP1 expression in adipocytes and preadipocytes. Surprisingly, this occurs through a mechanism independent of adipogenesis and involves FGF receptor-3 (FGFR3), prostaglandin-E2 and interaction between estrogen receptor-related alpha, flightless-1 (FLII) and leucine-rich-repeat-(in FLII)-interacting-protein-1 as a regulatory complex for UCP1 transcription. Physiologically, FGF6/9 expression in adipose is upregulated by exercise and cold in mice, and FGF9/FGFR3 expression in human neck fat is significantly associated with UCP1 expression. Loss of FGF9 impairs BAT thermogenesis. In vivo administration of FGF9 increases UCP1 expression and thermogenic capacity. Thus, FGF6 and FGF9 are adipokines that can regulate UCP1 through a transcriptional network that is dissociated from brown adipogenesis, and act to modulate systemic energy metabolism.

Suggested Citation

  • Farnaz Shamsi & Ruidan Xue & Tian Lian Huang & Morten Lundh & Yang Liu & Luiz O. Leiria & Matthew D. Lynes & Elena Kempf & Chih-Hao Wang & Satoru Sugimoto & Pasquale Nigro & Kathrin Landgraf & Tim Sch, 2020. "FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15055-9
    DOI: 10.1038/s41467-020-15055-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-15055-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-15055-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Tatsuya Yoshizawa & Yoshifumi Sato & Shihab U. Sobuz & Tomoya Mizumoto & Tomonori Tsuyama & Md. Fazlul Karim & Keishi Miyata & Masayoshi Tasaki & Masaya Yamazaki & Yuichi Kariba & Norie Araki & Eiichi, 2022. "SIRT7 suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15055-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.