FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis

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 Schulz, Yiming Li, Brice Emanuelli, Srinivas Kothakota, Lewis T. Williams, Niels Jessen, Steen Bønløkke Pedersen, Yvonne Böttcher, Matthias Blüher, Antje Körner, Laurie J. Goodyear, Moosa Mohammadi, C. Ronald Kahn and Yu-Hua Tseng ()
Additional contact information
Farnaz Shamsi: Harvard Medical School
Ruidan Xue: Harvard Medical School
Tian Lian Huang: Harvard Medical School
Morten Lundh: Harvard Medical School
Yang Liu: New York University School of Medicine
Luiz O. Leiria: Harvard Medical School
Matthew D. Lynes: Harvard Medical School
Elena Kempf: Harvard Medical School
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
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
Steen Bønløkke Pedersen: Aarhus University Hospital
Yvonne Böttcher: University of Oslo
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

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15055-9 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:11:y:2020:i:1:d:10.1038_s41467-020-15055-9

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

DOI: 10.1038/s41467-020-15055-9

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 ().