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

ABSTRACT: 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 ?Klotho functions as a coreceptor for FGF21 in vitro. To determine if ?Klotho is required for FGF21 action in vivo, we generated whole-body and adipose tissue-selective ?Klotho-knockout mice. All of the effects of FGF21 on growth and metabolism were lost in whole-body ?Klotho-knockout mice. Selective elimination of ?Klotho in adipose tissue blocked the acute insulin-sensitizing effects of FGF21. Taken together, these data demonstrate that ?Klotho is essential for FGF21 activity and that ?Klotho in adipose tissue contributes to the beneficial metabolic actions of FGF21.

SUBMITTER: Ding X

PROVIDER: S-EPMC3447537 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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

Ding Xunshan X Boney-Montoya Jamie J Owen Bryn M BM Bookout Angie L AL Coate Katie Colbert KC Mangelsdorf David J DJ Kliewer Steven A SA

Cell metabolism 20120901 3

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 m ...[more]

PMID: 22958921

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Agonistic ?-Klotho antibody mimics fibroblast growth factor 21 (FGF21) functions.

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