βKslotho is required for fibroblast growth factor 21 effects on growth and metabolism

Xunshan Ding, Jamie Boney-Montoya, Bryn M. Owen, Angie L. Bookout, Katie Colbert Coate, David J. Mangelsdorf, Steven A. Kliewer

Research output: Contribution to journalArticlepeer-review

239 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)387-393
Number of pages7
JournalCell Metabolism
Volume16
Issue number3
DOIs
StatePublished - Sep 5 2012

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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