FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis
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FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis. / Shamsi, Farnaz; Xue, Ruidan; Huang, Tian Lian; Lundh, Morten; Liu, Yang; Leiria, Luiz O.; Lynes, Matthew D.; Kempf, Elena; Wang, Chih Hao; Sugimoto, Satoru; Nigro, Pasquale; Landgraf, Kathrin; Schulz, Tim; Li, Yiming; Emanuelli, Brice; Kothakota, Srinivas; Williams, Lewis T.; Jessen, Niels; Pedersen, Steen Bønløkke; Böttcher, Yvonne; Blüher, Matthias; Körner, Antje; Goodyear, Laurie J.; Mohammadi, Moosa; Kahn, C. Ronald; Tseng, Yu Hua.
In: Nature Communications, Vol. 11, No. 1, 1421, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis
AU - Shamsi, Farnaz
AU - Xue, Ruidan
AU - Huang, Tian Lian
AU - Lundh, Morten
AU - Liu, Yang
AU - Leiria, Luiz O.
AU - Lynes, Matthew D.
AU - Kempf, Elena
AU - Wang, Chih Hao
AU - Sugimoto, Satoru
AU - Nigro, Pasquale
AU - Landgraf, Kathrin
AU - Schulz, Tim
AU - Li, Yiming
AU - Emanuelli, Brice
AU - Kothakota, Srinivas
AU - Williams, Lewis T.
AU - Jessen, Niels
AU - Pedersen, Steen Bønløkke
AU - Böttcher, Yvonne
AU - Blüher, Matthias
AU - Körner, Antje
AU - Goodyear, Laurie J.
AU - Mohammadi, Moosa
AU - Kahn, C. Ronald
AU - Tseng, Yu Hua
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-020-15055-9
DO - 10.1038/s41467-020-15055-9
M3 - Journal article
C2 - 32184391
AN - SCOPUS:85082023290
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1421
ER -
ID: 239203779