βKlotho Is Required for Fibroblast Growth Factor 21 Effects on Growth and Metabolism

被引：334

作者：

Ding, Xunshan ^{[1
,2
]}

Boney-Montoya, Jamie ^{[2
]}

Owen, Bryn M. ^{[1
]}

Bookout, Angie L. ^{[1
,3
]}

Coate, Katie Colbert ^{[1
,4
]}

Mangelsdorf, David J. ^{[1
,4
]}

Kliewer, Steven A. ^{[1
,2
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hypothalam Res, Dallas, TX 75390 USA

[4] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

来源：

CELL METABOLISM | 2012年 / 16卷 / 03期

基金：

美国国家卫生研究院;

关键词：

INCREASES ENERGY-EXPENDITURE; ACTIVATED-RECEPTOR-GAMMA; PPAR-ALPHA; INSULIN SENSITIVITY; ADIPOSE-TISSUE; FGF21; MICE; FIBROBLAST-GROWTH-FACTOR-21; EXPRESSION; SYSTEM;

D O I：

10.1016/j.cmet.2012.08.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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

引用

页码：387 / 393

页数：7

共 34 条

[1]

Badman MK, 2007, CELL METAB, V5, P426, DOI 10.1016/j.cmet.2007.05.002

[2] Fibroblast Growth Factor 21-Deficient Mice Demonstrate Impaired Adaptation to Ketosis [J].

Badman, Michael K. ;

Koester, Anja ;

Flier, Jeffrey S. ;

Kharitonenkov, Alexei ;

Maratos-Flier, Eleftheria .

ENDOCRINOLOGY, 2009, 150 (11) :4931-4940

[3] A CamKIIα iCre BAC allows brain-specific gene inactivation [J].

Casanova, E ;

Fehsenfeld, S ;

Mantamadiotis, T ;

Lemberger, T ;

Greiner, E ;

Stewart, AF ;

Schütz, G .

GENESIS, 2001, 31 (01) :37-42

[4] Brown Adipose Tissue Responds to Cold and Adrenergic Stimulation by Induction of FGF21 [J].

Chartoumpekis, Dionysios V. ;

Habeos, Ioannis G. ;

Ziros, Panos G. ;

Psyrogiannis, Agathoklis I. ;

Kyriazopoulou, Venetsana E. ;

Papavassiliou, Athanasios G. .

MOLECULAR MEDICINE, 2011, 17 (7-8) :736-740

[5] Fibroblast Growth Factor 21 Corrects Obesity in Mice [J].

Coskun, Tamer ;

Bina, Holly A. ;

Schneider, Michael A. ;

Dunbar, James D. ;

Hu, Charlie C. ;

Chen, Yanyun ;

Moller, David E. ;

Kharitonenkov, Alexei .

ENDOCRINOLOGY, 2008, 149 (12) :6018-6027

[6] Fibroblast Growth Factor-21 Regulates PPARγ Activity and the Antidiabetic Actions of Thiazolidinediones [J].

Dutchak, Paul A. ;

Katafuchi, Takeshi ;

Bookout, Angie L. ;

Choi, Jang Hyun ;

Yu, Ruth T. ;

Mangelsdorf, David J. ;

Kliewer, Steven A. .

CELL, 2012, 148 (03) :556-567

[7] FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis [J].

Fisher, Ffolliott M. ;

Kleiner, Sandra ;

Douris, Nicholas ;

Fox, Elliott C. ;

Mepani, Rina J. ;

Verdeguer, Francisco ;

Wu, Jun ;

Kharitonenkov, Alexei ;

Flier, Jeffrey S. ;

Maratos-Flier, Eleftheria ;

Spiegelman, Bruce M. .

GENES & DEVELOPMENT, 2012, 26 (03) :271-281

[8] Obesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State [J].

Fisher, Ffolliott M. ;

Chui, Patricia C. ;

Antonellis, Patrick J. ;

Bina, Holly A. ;

Kharitonenkov, Alexei ;

Flier, Jeffrey S. ;

Maratos-Flier, Eleftheria .

DIABETES, 2010, 59 (11) :2781-2789

[9] Thermogenic Activation Induces FGF21 Expression and Release in Brown Adipose Tissue [J].

Hondares, Elayne ;

Iglesias, Roser ;

Giralt, Albert ;

Gonzalez, Frank J. ;

Giralt, Marta ;

Mampel, Teresa ;

Villarroya, Francesc .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (15) :12983-12990

[10] Inhibition of growth hormone signaling by the fasting-induced hormone FGF21 [J].

Inagaki, Takeshi ;

Lin, Vicky Y. ;

Goetz, Regina ;

Mohammadi, Moosa ;

Mangelsdorf, David J. ;

Kliewer, Steven A. .

CELL METABOLISM, 2008, 8 (01) :77-83

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