Niels Jessen

FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Farnaz Shamsi, Harvard Medical School
  • ,
  • Ruidan Xue, Harvard Medical School, Fudan University
  • ,
  • Tian Lian Huang, Harvard Medical School
  • ,
  • Morten Lundh, Harvard Medical School, Københavns Universitet
  • ,
  • Yang Liu, New York University School of Medicine
  • ,
  • Luiz O Leiria, Harvard Medical School, 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, Københavns Universitet
  • ,
  • Srinivas Kothakota, Five Prime Therapeutics, San Francisco, CA, 94080, USA.
  • ,
  • Lewis T Williams, Five Prime Therapeutics, San Francisco, CA, 94080, USA.
  • ,
  • Niels Jessen
  • Steen Bønløkke Pedersen
  • Yvonne Böttcher, University of Oslo, Akershus University Hospital, 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

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.

OriginalsprogEngelsk
Artikelnummer1421
TidsskriftNature Communications
Vol/bind11
Nummer1
Antal sider16
ISSN2041-1723
DOI
StatusUdgivet - 2020

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