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βKlotho is required for fibroblast growth factor 21 effects on growth and metabolism.

Fibroblast growth factor 21 (FGF21) is a fasting-induced hepatokine that has potent pharmacologic effects in mice, which include improving insulin sensitivity and blunting growth. The single-transmembrane protein βKlotho functions as a coreceptor for FGF21 in vitro. To determine if βKlotho is required for FGF21 action in vivo, we generated whole-body and adipose tissue-selective βKlotho-knockout mice. All of the effects of FGF21 on growth and metabolism were lost in whole-body βKlotho-knockout mice. Selective elimination of βKlotho in adipose tissue blocked the acute insulin-sensitizing effects of FGF21. Taken together, these data demonstrate that βKlotho is essential for FGF21 activity and that βKlotho in adipose tissue contributes to the beneficial metabolic actions of FGF21.

Pubmed ID: 22958921

Authors

  • Ding X
  • Boney-Montoya J
  • Owen BM
  • Bookout AL
  • Coate KC
  • Mangelsdorf DJ
  • Kliewer SA

Journal

Cell metabolism

Publication Data

September 5, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: 1RL1GM084436-01
  • Agency: NIDDK NIH HHS, Id: DK067158
  • Agency: NIGMS NIH HHS, Id: GM007062
  • Agency: NCRR NIH HHS, Id: P20 RR020691
  • Agency: NCRR NIH HHS, Id: P20RR20691
  • Agency: NIDDK NIH HHS, Id: R01 DK067158
  • Agency: NIDDK NIH HHS, Id: R56 DK089600
  • Agency: NIGMS NIH HHS, Id: RL1 GM084436
  • Agency: NIGMS NIH HHS, Id: T32 GM007062
  • Agency: NIDDK NIH HHS, Id: U19 DK062434
  • Agency: NIDDK NIH HHS, Id: U19DK62434
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Adipose Tissue
  • Animals
  • Body Composition
  • Chromatography, Gel
  • Energy Metabolism
  • Fibroblast Growth Factors
  • Glucose Tolerance Test
  • Growth
  • Insulin Resistance
  • Membrane Proteins
  • Mice
  • Mice, Knockout