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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.
Affiliation
  • Shamsi F; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Xue R; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Huang TL; Division of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Lundh M; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Liu Y; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Leiria LO; The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
  • Lynes MD; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA.
  • Kempf E; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Wang CH; Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Sugimoto S; Center of Research of Inflammatory Diseases, Ribeirao Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Nigro P; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Landgraf K; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Schulz T; Center for Pediatric Research Leipzig, University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
  • Li Y; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Emanuelli B; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Kothakota S; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Williams LT; Center for Pediatric Research Leipzig, University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
  • Jessen N; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Pedersen SB; German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
  • Böttcher Y; Division of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Blüher M; The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
  • Körner A; Five Prime Therapeutics, San Francisco, CA, 94080, USA.
  • Goodyear LJ; Five Prime Therapeutics, San Francisco, CA, 94080, USA.
  • Mohammadi M; Steno Diabetes Center Aarhus, Aarhus University Hospital, 8200, Aarhus N, Denmark.
  • Kahn CR; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Tseng YH; Steno Diabetes Center Aarhus, Aarhus University Hospital, 8200, Aarhus N, Denmark.
Nat Commun ; 11(1): 1421, 2020 03 17.
Article in En | MEDLINE | ID: mdl-32184391
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fibroblast Growth Factor 6 / Fibroblast Growth Factor 9 / Adipogenesis / Adipocytes, Brown / Uncoupling Protein 1 / Obesity Type of study: Prognostic_studies Limits: Animals / Humans / Male Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Document type: Article Affiliation country: United States Publication country: ENGLAND / ESCOCIA / GB / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fibroblast Growth Factor 6 / Fibroblast Growth Factor 9 / Adipogenesis / Adipocytes, Brown / Uncoupling Protein 1 / Obesity Type of study: Prognostic_studies Limits: Animals / Humans / Male Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Document type: Article Affiliation country: United States Publication country: ENGLAND / ESCOCIA / GB / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM