title: βKlotho 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 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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Xunshan
authors.initials: X
authors.lastname: Ding
authors.forename: Jamie
authors.initials: J
authors.lastname: Boney-Montoya
authors.forename: Bryn M
authors.initials: BM
authors.lastname: Owen
authors.forename: Angie L
authors.initials: AL
authors.lastname: Bookout
authors.forename: Katie Colbert
authors.initials: KC
authors.lastname: Coate
authors.forename: David J
authors.initials: DJ
authors.lastname: Mangelsdorf
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kliewer
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D002850:Chromatography, Gel; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D005951:Glucose Tolerance Test; D006128:Growth / Q000235:genetics / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D000090265:Klotho Proteins; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout
chemical_list: C418622:Klb protein, mouse; D008565:Membrane Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D000090265:Klotho Proteins