βKlotho Is Required for Fibroblast Growth Factor (FGF) 21 Signaling through FGF Receptor (FGFR) 1c and FGFR3c
Open accessAbstract
Fibroblast growth factor (FGF) 21, a structural relative of FGF23 that regulates phosphate homeostasis, is a regulator of insulin-independent glucose transport in adipocytes and plays a role in the regulation of body weight. It also regulates ketogenesis and adaptive responses to starvation. We report that in a reconstituted receptor activation assay system using BaF3 cells, which do not endogenously express any type of FGF receptor (FGFR) or heparan sulfate proteoglycan, FGF21 alone does not activate FGFRs and that betaKlotho is required for FGF21 to activate two specific FGFR subtypes: FGFR1c and FGFR3c. Coexpression of betaKlotho and FGFR1c on BaF3 cells enabled FGF21, but not FGF23, to activate receptor signaling. Conversely, coexpression of FGFR1c and Klotho, a protein related to betaKlotho, enabled FGF23 but not FGF21 to activate receptor signaling, indicating that expression of betaKlotho/Klotho confers target cell specificity on FGF21/FGF23. In all of these cases, heparin enhanced the activation but was not essential. In 3T3-L1 adipocytes, up-regulation of glucose transporter (GLUT) expression by FGF21 was associated with expression of betaKlotho, which was absent in undifferentiated 3T3-L1 fibroblasts. It is thus suggested that betaKlotho expression is a crucial determinant of the FGF21 specificity of the target cells upon which it acts in an endocrine fashion.
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FGF21 signals by binding and activating a receptor complex composed of KLB and FGFR1c.
“FGF21 elicits its biological effects by binding and activating a receptor complex composed of the co-receptor KLB and a traditional FGF receptor, fibroblast growth factor receptor 1c (FGFR1c)46,47.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [47]
FGF21 signals to a receptor complex comprised of FGFR1c and KLB.
“FGF21 signals to a receptor complex comprised of FGF receptor 1c (FGFR1c) and its co-receptor β-klotho (KLB) [[143], [144], [145], [146]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [144]
FGF21 functions in target tissues that express FGFR1c and the obligate coreceptor β-klotho.
“FGF21 functions in target tissues that express the traditional FGF receptor FGFR1c and the obligate coreceptor β-klotho (2, 27, 71, 99, 124, 140).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [124]
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
FGF-21 as a novel metabolic regulator
Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23606 · Cited by 2,125 · see citing works
Ornitz, D. M., & Itoh, N. (2001) · Genome biology · doi:10.1186/gb-2001-2-3-reviews3005 · Cited by 1,985 · see citing works
Cellular signaling by fibroblast growth factor receptors
Eswarakumar, V. P., Lax, I., & Schlessinger, J. (2005) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.01.001 · Cited by 1,923 · see citing works
Receptor Specificity of the Fibroblast Growth Factor Family
Ornitz, D. M., Xu, J., Colvin, J. S., McEwen, D. G., MacArthur, C. A., Coulier, F., Gao, G., & Goldfarb, M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.15292 · Cited by 1,871 · see citing works
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.001 · Cited by 1,865 · see citing works
Klotho converts canonical FGF receptor into a specific receptor for FGF23
Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S., & Yamashita, T. (2006) · Nature · doi:10.1038/nature05315 · Cited by 1,846 · see citing works
Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504 · see citing works
Shimada, T., Kakitani, M., Yamazaki, Y., Hasegawa, H., Takeuchi, Y., Fujita, T., Fukumoto, S., Tomizuka, K., & Yamashita, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19081 · Cited by 1,503 · see citing works
Badman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495 · see citing works
Shimada, T., Kakitani, M., Yamazaki, Y., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419081 · Cited by 1,368 · see citing works
Regulation of Fibroblast Growth Factor-23 Signaling by Klotho*
Kurosu, H., Ogawa, Y., Miyoshi, M., Yamamoto, M., Nandi, A., Rosenblatt, K., Baum, M., Schiavi, S., Hu, M.-C., Moe, O., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.c500457200 · Cited by 1,356 · see citing works
Receptor Specificity of the Fibroblast Growth Factor Family
Zhang, X., Ibrahimi, O. A., Olsen, S. K., Umemori, H., Mohammadi, M., & Ornitz, D. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601252200 · Cited by 1,164 · see citing works
Evolution of the Fgf and Fgfr gene families.
Itoh, N., & Ornitz, D. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.08.007 · Cited by 1,123 · see citing works
Identification of a novel FGF, FGF-21, preferentially expressed in the liver
Nishimura, T., Nakatake, Y., Konishi, M., & Itoh, N. (2000) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(00)00067-1 · Cited by 847 · see citing works
Kurosu, H., Choi, M., Ogawa, Y., Dickson, A. S., Goetz, R., Eliseenkova, A. V., Mohammadi, M., Rosenblatt, K. P., Kliewer, S. A., & Kuro-o, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704165200 · Cited by 748 · see citing works
Holt, J. A., Luo, G., Billin, A. N., Bisi, J., McNeill, Y. Y., Kozarsky, K., Donahee, M. H., Wang, D. Y., Mansfield, T. A., Kliewer, S. A., et al. (2003) · Genes & Development · doi:10.1101/gad.1083503 · Cited by 698 · see citing works
βKlotho is required for metabolic activity of fibroblast growth factor 21
Ogawa, Y., Kurosu, H., Yamamoto, M., Nandi, A., Rosenblatt, K. P., Goetz, R., Eliseenkova, A. V., Mohammadi, M., & Kuro-o, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701600104 · Cited by 617 · see citing works
Wente, W., Efanov, A. M., Brenner, M. B., Kharitonenkov, A., Koster, A. M., Sandusky, G. E., Sewing, S., Treinies, I., Zitzer, H., & Gromada, J. (2006) · Diabetes · doi:10.2337/db05-1435 · Cited by 497 · see citing works
Shimada, T., Muto, T., Urakawa, I., Yoneya, T., Yamazaki, Y., Okawa, K., Takeuchi, Y., Fujita, T., Fukumoto, S., & Yamashita, T. (2002) · Endocrinology · doi:10.1210/endo.143.8.8795 · Cited by 439 · see citing works
FGF‐21/FGF‐21 receptor interaction and activation is determined by βKlotho
Kharitonenkov, A., Dunbar, J. D., Bina, H. A., Bright, S. W., Moyers, J. S., Zhang, C., Ding, L., Micanovic, R., Mehrbod, S. F., Knierman, M. D., et al. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21357 · Cited by 329 · see citing works
Ito, S., Kinoshita, S., Shiraishi, N., Nakagawa, S., Sekine, S., Fujimori, T., & Nabeshima, Y. (2000) · Mechanisms of Development · doi:10.1016/s0925-4773(00)00439-1 · Cited by 312 · see citing works
Impaired negative feedback suppression of bile acid synthesis in mice lacking βKlotho
Ito, S., Fujimori, T., Furuya, A., Satoh, J., Nabeshima, Y., & Nabeshima, Y. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23076 · Cited by 248 · see citing works
Yoshida, T., Fujimori, T., & Nabeshima, Y. (2002) · Endocrinology · doi:10.1210/endo.143.2.8657 · Cited by 240 · see citing works
Molecular determinants of FGF‐21 activity—synergy and cross‐talk with PPARγ signaling
Moyers, J. S., Shiyanova, T. L., Mehrbod, F., Dunbar, J. D., Noblitt, T. W., Otto, K. A., Reifel-Miller, A. E., & Kharitonenkov, A. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20847 · Cited by 193 · see citing works
Lax, I., Wong, A., Lamothe, B., Lee, A., Frost, A. S., Hawes, J. J., & Schlessinger, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00689-5 · Cited by 166 · see citing works
Role of heparan sulfate as a tissue-specific regulator of FGF-4 and FGF receptor recognition
Allen, B. L., Filla, M. S., & Rapraeger, A. C. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200106075 · Cited by 154 · see citing works
FGF23 and disorders of phosphate homeostasis.
Yu, X.-J., & White, K. (2005) · Cytokine & growth factor reviews · doi:10.1016/j.cytogfr.2005.01.002 · Cited by 138 · see citing works
Komi-Kuramochi, A., Kawano, M., Oda, Y., Asada, M., Suzuki, M., Oki, J., & Imamura, T. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.06055 · Cited by 138 · see citing works
Self-citationCheung, W.-F., Eriksson, I., Kusche‐Gullberg, M., Lindahl, U., & Kjellén, L. (1996) · Biochemistry · doi:10.1021/bi952325b · Cited by 53 · see citing works
Altered collagen and glycosaminoglycan secretion by a skeletal muscle myoblast variant.
Schubert, D. A., & LaCorbiere, M. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)70326-3 · Cited by 18 · see citing works
Uruno, T., Oki, J., Ozawa, K., Miyakawa, K., Ueno, H., & Imamura, T. (1999) · Growth Factors · doi:10.3109/08977199909103519 · Cited by 12 · see citing works
Self-citationKurata, K., & Suyama, A. (1999) · doi:10.11234/gi1990.10.225 · Cited by 7 · see citing works
Construction of pcDNA3.1-based vectors with blasticidin and puromycin resistance markers
Asada, M., Honda, E., & Imamura, T. (2006) · Analytical Biochemistry · doi:10.1016/j.ab.2006.03.017 · Cited by 5 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Fibroblast Growth Factor signaling pathway
Ornitz, D. M., & Itoh, N. (2015) · WIREs Developmental Biology · doi:10.1002/wdev.176 · Cited by 2,050 · see citing works
The FGF family: biology, pathophysiology and therapy
Beenken, A., & Mohammadi, M. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2792 · Cited by 1,945 · see citing works
Fibroblast Growth Factor 21 Corrects Obesity in Mice
Coskun, T., Bina, H. A., Schneider, M. A., Dunbar, J. D., Hu, C. C., Chen, Y., Moller, D. E., & Kharitonenkov, A. (2008) · Endocrinology · doi:10.1210/en.2008-0816 · Cited by 1,031 · see citing works
Understanding the Physiology of FGF21
Fisher, F. M., & Maratos-Flier, E. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105339 · Cited by 912 · see citing works
The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways
Houtkooper, R. H., Cantó, C., Wanders, R. J., & Auwerx, J. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0026 · Cited by 899 · see citing works
Obesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State
Fisher, F. M., Chui, P. C., Antonellis, P. J., Bina, H. A., Kharitonenkov, A., Flier, J. S., & Maratos-Flier, E. (2010) · Diabetes · doi:10.2337/db10-0193 · Cited by 830 · see citing works
Potthoff, M. J., Inagaki, T., Satapati, S., Ding, X., He, T., Goetz, R., Mohammadi, M., Finck, B. N., Mangelsdorf, D. J., Kliewer, S. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904187106 · Cited by 704 · see citing works
Fon Tacer, K., Bookout, A. L., Ding, X., Kurosu, H., John, G. B., Wang, L., Goetz, R., Mohammadi, M., Kuro-o, M., Mangelsdorf, D. J., et al. (2010) · Molecular Endocrinology · doi:10.1210/me.2010-0142 · Cited by 700 · see citing works
Lin, Z., Tian, H., Lam, K. S. L., Lin, S., Hoo, R. C. L., Konishi, M., Itoh, N., Wang, Y., Bornstein, S. R., Xu, A., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.005 · Cited by 691 · see citing works
Molecular Basis of Klotho: From Gene to Function in Aging
Xu, Y., & Sun, Z. (2015) · Endocrine Reviews · doi:10.1210/er.2013-1079 · Cited by 550 · see citing works
FGF21 regulates metabolism and circadian behavior by acting on the nervous system
Bookout, A. L., de Groot, M. H. M., Owen, B. M., Lee, S., Gautron, L., Lawrence, H. L., Ding, X., Elmquist, J. K., Takahashi, J. S., Mangelsdorf, D. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3249 · Cited by 545 · see citing works
Dutchak, P. A., Katafuchi, T., Bookout, A. L., Choi, J. H., Yu, R. T., Mangelsdorf, D. J., & Kliewer, S. A. (2012) · Cell · doi:10.1016/j.cell.2011.11.062 · Cited by 537 · see citing works
α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling
Chen, G., Yang, L., Goetz, R. M., Fu, L., Jayaraman, S., Hu, M. C., Moe, O. W., Liang, G., Li, X., & Mohammadi, M. (2018) · Nature · doi:10.1038/nature25451 · Cited by 491 · see citing works
Endocrine functions of bone in mineral metabolism regulation
Quarles, L. D. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36479 · Cited by 459 · see citing works
Endocrine fibroblast growth factors 15/19 and 21: from feast to famine
Potthoff, M. J., Kliewer, S. A., & Mangelsdorf, D. J. (2012) · Genes & Development · doi:10.1101/gad.184788.111 · Cited by 442 · see citing works
Inhibition of Growth Hormone Signaling by the Fasting-Induced Hormone FGF21
Inagaki, T., Lin, V. Y., Goetz, R., Mohammadi, M., Mangelsdorf, D. J., & Kliewer, S. A. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.05.006 · Cited by 409 · see citing works
βKlotho Is Required for Fibroblast Growth Factor 21 Effects on Growth and Metabolism
Ding, X., Boney-Montoya, J., Owen, B. M., Bookout, A. L., Coate, K. C., Mangelsdorf, D. J., & Kliewer, S. A. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.002 · Cited by 403 · see citing works
Fibroblast Growth Factor 21-Deficient Mice Demonstrate Impaired Adaptation to Ketosis
Badman, M. K., Koester, A., Flier, J. S., Kharitonenkov, A., & Maratos-Flier, E. (2009) · Endocrinology · doi:10.1210/en.2009-0532 · Cited by 362 · see citing works
Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication
Funcke, J., & Scherer, P. E. (2019) · Journal of Lipid Research · doi:10.1194/jlr.r094060 · Cited by 337 · see citing works
Flippo, K. H., & Potthoff, M. J. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00354-2 · Cited by 311 · see citing works
Berglund, E. D., Li, C. Y., Bina, H. A., Lynes, S. E., Michael, M. D., Shanafelt, A. B., Kharitonenkov, A., & Wasserman, D. H. (2009) · Endocrinology · doi:10.1210/en.2009-0221 · Cited by 297 · see citing works
Sarruf, D. A., Thaler, J. P., Morton, G. J., German, J. P., Fischer, J. D., Ogimoto, K., & Schwartz, M. W. (2010) · Diabetes · doi:10.2337/db09-1878 · Cited by 287 · see citing works
Fibroblast Growth Factor 21—Metabolic Role in Mice and Men
Staiger, H., Keuper, M., Berti, L., Hrabě de Angelis, M., & Häring, H.-U. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00016 · Cited by 270 · see citing works
Molecular Mechanisms of Fibroblast Growth Factor Signaling in Physiology and PathologyPreprint
Belov, A. A., & Mohammadi, M. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a015958 · Cited by 272 · see citing works
Martin, A., Liu, S., David, V., Li, H., Karydis, A., Feng, J. Q., & Quarles, L. D. (2011) · The FASEB Journal · doi:10.1096/fj.10-177816 · Cited by 254 · see citing works
Hepatokines and metabolism: Deciphering communication from the liver
Jensen-Cody, S. O., & Potthoff, M. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101138 · Cited by 252 · see citing works
Brown Adipose Tissue Responds to Cold and Adrenergic Stimulation by Induction of FGF21
Chartoumpekis, D. V., Habeos, I. G., Ziros, P. G., Psyrogiannis, A. I., Kyriazopoulou, V. E., & Papavassiliou, A. G. (2011) · Molecular Medicine · doi:10.2119/molmed.2011.00075 · Cited by 252 · see citing works
Interplay between FGF21 and insulin action in the liver regulates metabolism
Emanuelli, B., Vienberg, S. G., Smyth, G., Cheng, C., Stanford, K. I., Arumugam, M., Michael, M. D., Adams, A. C., Kharitonenkov, A., & Kahn, C. R. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67353 · Cited by 243 · see citing works
Itoh, N. (2010) · Cell and Tissue Research · doi:10.1007/s00441-010-1024-2 · Cited by 247 · see citing works
Integrated Regulation of Hepatic Metabolism by Fibroblast Growth Factor 21 (FGF21) in Vivo
Fisher, F. M., Estall, J. L., Adams, A. C., Antonellis, P. J., Bina, H. A., Flier, J. S., Kharitonenkov, A., Spiegelman, B. M., & Maratos–Flier, E. (2011) · Endocrinology · doi:10.1210/en.2011-0281 · Cited by 229 · see citing works
Mashili, F. L., Austin, R. L., Deshmukh, A. S., Fritz, T., Caidahl, K., Bergdahl, K., Zierath, J. R., Chibalin, A., Moller, D. E., Kharitonenkov, A., et al. (2011) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.1177 · Cited by 222 · see citing works
Fibroblast growth factor 21: from pharmacology to physiology
Kliewer, S. A., & Mangelsdorf, D. J. (2010) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.28449b · Cited by 219 · see citing works
Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis
BonDurant, L. D., & Potthoff, M. J. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064800 · Cited by 222 · see citing works
Klotho/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease
Lü, X., & Hu, M. C. (2016) · Kidney Diseases · doi:10.1159/000452880 · Cited by 220 · see citing works
Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice
Douris, N., Stevanovic, D. M., Fisher, F. M., Cisu, T. I., Chee, M. J., Nguyen, N. L., Zarebidaki, E., Adams, A. C., Kharitonenkov, A., Flier, J. S., et al. (2015) · Endocrinology · doi:10.1210/en.2014-2001 · Cited by 215 · see citing works
Foltz, I. N., Hu, S., King, C., Wu, X., Yang, C., Wang, W., Weiszmann, J., Stevens, J., Chen, J. S., Nuanmanee, N., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004690 · Cited by 211 · see citing works
Gallego-Escuredo, J. M., Gómez‐Ambrosi, J., Catalán, V., Domingo, P., Giralt, M., Frühbeck, G., & Villarroya, F. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.76 · Cited by 212 · see citing works
Phosphate homeostasis and the renal-gastrointestinal axis
Marks, J., Debnam, E. S., & Unwin, R. J. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00508.2009 · Cited by 209 · see citing works
Biomarkers of insulin sensitivity and insulin resistance: Past, present and future
Park, S. E., Park, C., & Sweeney, G. (2015) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2015.1023429 · Cited by 209 · see citing works
The Klotho gene family as a regulator of endocrine fibroblast growth factors.
Kurosu, H., & Kuro-o, M. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.10.052 · Cited by 196 · see citing works
Inventing new medicines: The FGF21 story
Kharitonenkov, A., & Adams, A. C. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2013.12.003 · Cited by 198 · see citing works
Díaz-Delfín, J., Hondares, E., Iglesias, R., Giralt, M., Caelles, C., & Villarroya, F. (2012) · Endocrinology · doi:10.1210/en.2012-1193 · Cited by 195 · see citing works
Wu, A.-L., Coulter, S., Liddle, C., Wong, A., Eastham‐Anderson, J., French, D. M., Peterson, A. S., & Sonoda, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017868 · Cited by 185 · see citing works
Nrf2 Represses FGF21 During Long-Term High-Fat Diet–Induced Obesity in Mice
Chartoumpekis, D. V., Ziros, P. G., Psyrogiannis, A. I., Papavassiliou, A. G., Kyriazopoulou, V. E., Sykiotis, G. P., & Habeos, I. G. (2011) · Diabetes · doi:10.2337/db11-0112 · Cited by 184 · see citing works
Ge, X., Chen, C., Hui, X. H., Wang, Y., Lam, K. S. L., & Xu, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.248591 · Cited by 181 · see citing works
Yu, Y.-H., He, J., Li, S., Song, L., Guo, X., Yao, W., Zou, D., Gao, X., Liu, Y., Bai, F., et al. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.05.026 · Cited by 181 · see citing works
FGF21 Requires βklotho to Act In Vivo
Adams, A. C., Cheng, C. C., Coskun, T., & Kharitonenkov, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049977 · Cited by 181 · see citing works
Endocrine Protection of Ischemic Myocardium by FGF21 from the Liver and Adipose Tissue
Liu, S. Q., Roberts, D., Kharitonenkov, A., Zhang, B., Hanson, S., Li, Y. C., Zhang, L., & Wu, Y. (2013) · Scientific Reports · doi:10.1038/srep02767 · Cited by 179 · see citing works
αKlotho Mitigates Progression of AKI to CKD through Activation of Autophagy
Shi, M., Flores, B., Gillings, N., Bian, A., Cho, H. J., Yan, S. X., Liu, Y., Levine, B., Moe, O. W., & Hu, M. C. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015060613 · Cited by 179 · see citing works
Differential Specificity of Endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in Complex with KLB
Yang, C., Jin, C., Li, X., Wang, F., McKeehan, W. L., & Luo, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033870 · Cited by 173 · see citing works
Rational Design of a Fibroblast Growth Factor 21-Based Clinical Candidate, LY2405319
Kharitonenkov, A., Beals, J. M., Micanovic, R., Strifler, B. A., Rathnachalam, R., Wroblewski, V. J., Li, S., Köester, A., Ford, A. M., Coşkun, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058575 · Cited by 168 · see citing works
Going Back to the Biology of FGF21: New Insights
Lewis, J. E., Ebling, F. J. P., Samms, R. J., & Tsintzas, K. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.05.007 · Cited by 164 · see citing works
Mu, J., Pinkstaff, J. K., Li, Z., Skidmore, L. K., Li, N., Myler, H. A., Dallas-Yang, Q., Hays, A. A., Yao, J., Bussell, S., et al. (2011) · Diabetes · doi:10.2337/db11-0838 · Cited by 162 · see citing works
Wang, Q., Yuan, J., Yu, Z., Lin, L., Jiang, Y., Cao, Z., Zhuang, P., Whalen, M. J., Song, B., Wang, X., et al. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0663-7 · Cited by 157 · see citing works
Christodoulides, C., Dyson, P., Sprecher, D., Tsintzas, K., & Karpe, F. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0111 · Cited by 153 · see citing works
FGF21 N‐ and C‐termini play different roles in receptor interaction and activation
Yie, J., Hecht, R., Patel, J., Stevens, J., Wang, W., Hawkins, N., Steavenson, S., Smith, S., Winters, D., Fisher, S., et al. (2009) · FEBS Letters · doi:10.1016/j.febslet.2008.11.023 · Cited by 149 · see citing works
FGF21: A Novel Regulator of Glucose and Lipid Metabolism and Whole-Body Energy Balance
Szczepańska, E., & Gietka‐Czernel, M. (2022) · Hormone and Metabolic Research · doi:10.1055/a-1778-4159 · Cited by 155 · see citing works
FGF21 reloaded: challenges of a rapidly growing field
Kharitonenkov, A., & Larsen, P. J. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.11.003 · Cited by 147 · see citing works
Different roles of N‐ and C‐ termini in the functional activity of FGF21
Micanovic, R., Raches, D. W., Dunbar, J. D., Driver, D. A., Bina, H. A., Dickinson, C. D., & Kharitonenkov, A. (2009) · Journal of Cellular Physiology · doi:10.1002/jcp.21675 · Cited by 146 · see citing works
Relevant use of Klotho in FGF19 subfamily signaling system in vivo
Tomiyama, K.-I., Maeda, R., Urakawa, I., Yamazaki, Y., Tanaka, T., Ito, S., Nabeshima, Y., Tomita, T., Odori, S., Hosoda, K., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913986107 · Cited by 143 · see citing works
FGF21 Promotes Metabolic Homeostasis via White Adipose and Leptin in Mice
Véniant, M. M., Hale, C., Helmering, J., Chen, M. M., Stanislaus, S., Busby, J., Vonderfecht, S., Xu, J., & Lloyd, D. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040164 · Cited by 141 · see citing works
Pan, Q., Lin, S., Li, Y., Liu, L., Li, X., Gao, X., Yan, J., Gu, B., Chen, X., Li, W., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.103202 · Cited by 138 · see citing works
Endocrine FGFs and Klothos: emerging concepts.
Kuro-o, M. (2008) · Trends in endocrinology and metabolism · doi:10.1016/j.tem.2008.06.002 · Cited by 154 · see citing works
Fibroblast Growth Factor Signaling in Metabolic Regulation
Nies, V. J. M., Sancar, G., Liu, W., van Zutphen, T., Struik, D., Yu, R. T., Atkins, A. R., Evans, R. M., Jonker, J. W., & Downes, M. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00193 · Cited by 135 · see citing works
Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling
Ferguson, H. R., Smith, M. P., & Francavilla, C. (2021) · Cells · doi:10.3390/cells10051201 · Cited by 137 · see citing works
Circulating FGF21 proteolytic processing mediated by fibroblast activation protein
Zhen, E. Y., Jin, Z., Ackermann, B. L., Thomas, M. K., & Gutierrez, J. A. (2016) · Biochemical Journal · doi:10.1042/bj20151085 · Cited by 123 · see citing works
Ortíz, M., Soto-Alarcón, S. A., Orellana, P., Espinosa, A., Campos, C., López‐Arana, S., Rincón‐Cervera, M. Á., Illesca, P., Valenzuela, R., & Videla, L. A. (2020) · Digestive and Liver Disease · doi:10.1016/j.dld.2020.04.019 · Cited by 124 · see citing works
Pathophysiological roles of FGF signaling in the heart
Itoh, N., & Ohta, H. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00247 · Cited by 122 · see citing works
Huang, J., Ishino, T., Chen, G., Rolzin, P., Osothprarop, T. F., Retting, K., Li, L., Jin, P., Matin, M. J., Huyghe, B., et al. (2013) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.204420 · Cited by 121 · see citing works
Regulation of longevity by FGF21: interaction between energy metabolism and stress responses
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.05.004 · Cited by 121 · see citing works
Wang, Z., Leng, Y., Wang, J., Liao, H.-M., Bergman, J. A., Leeds, P. R., Kozikowski, A. P., & Chuang, D. (2016) · Scientific Reports · doi:10.1038/srep19626 · Cited by 119 · see citing works
Assini, J. M., Mulvihill, E. E., Burke, A. C., Sutherland, B. G., Telford, D. E., Chhoker, S. S., Sawyez, C. G., Drangova, M., Adams, A. C., Kharitonenkov, A., et al. (2015) · Endocrinology · doi:10.1210/en.2014-2003 · Cited by 119 · see citing works
The role of Klotho in energy metabolism
Razzaque, M. S. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.75 · Cited by 117 · see citing works
Activation of Liver FGF21 in hepatocarcinogenesis and during hepatic stress
Yang, C., Lu, W., Lin, T., You, P., Ye, M., Huang, Y., Jiang, X., Wang, C., Wang, F., Lee, M., et al. (2013) · BMC Gastroenterology · doi:10.1186/1471-230x-13-67 · Cited by 117 · see citing works
Mäkelä, J., Tselykh, T. V., Maiorana, F., Eriksson, O., Thi, H., Mudò, G., Korhonen, L., Belluardo, N., & Lindholm, D. (2014) · SpringerPlus · doi:10.1186/2193-1801-3-2 · Cited by 116 · see citing works
Glycosaminoglycan affinity of the complete fibroblast growth factor family
Asada, M., Shinomiya, M., Suzuki, M., Honda, E., Sugimoto, R., Ikekita, M., & Imamura, T. (2008) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.09.001 · Cited by 116 · see citing works
Self-citationMammary Gland Growth Factors: Roles in Normal Development and in CancerPreprint
Hynes, N. E., & Watson, C. J. E. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003186 · Cited by 113 · see citing works
Zhang, C., Huang, Z., Gu, J., Yan, X., Lu, X., Zhou, S., Wang, S., Shao, M., Zhang, F., Cheng, P., et al. (2015) · Diabetologia · doi:10.1007/s00125-015-3630-8 · Cited by 113 · see citing works
Osteocyte-Specific Deletion of Fgfr1 Suppresses FGF23
Xiao, Z., Huang, J., Cao, L., Liang, Y., Han, X., & Quarles, L. D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104154 · Cited by 113 · see citing works
Iglesias, P., Selgas, R., Romero, S., & Díez, J. J. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0357 · Cited by 113 · see citing works
Fundamentals of FGF19 & FGF21 Action In Vitro and In Vivo
Adams, A. C., Coskun, T., Irizarry Rovira, A. R., Schneider, M. A., Raches, D. W., Micanovic, R., Bina, H. A., Dunbar, J. D., & Kharitonenkov, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038438 · Cited by 109 · see citing works
Li, X., Ge, H., Weiszmann, J., Hecht, R. I., Li, Y., Véniant, M. M., Xu, J., Wu, X., Lindberg, R. A., & Li, Y. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.09.012 · Cited by 107 · see citing works
So, W. Y., Cheng, Q., Chen, L., Evans‐Molina, C., Xu, A., Lam, K. S. L., & Leung, P. S. (2013) · Diabetes · doi:10.2337/db13-0645 · Cited by 109 · see citing works
Uncoupling the Mitogenic and Metabolic Functions of FGF1 by Tuning FGF1-FGF Receptor Dimer Stability
Huang, Z., Tan, Y., Gu, J., Liu, Y., Song, L., Niu, J., Zhao, L., Srinivasan, L., Lin, Q., Deng, J., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.06.063 · Cited by 103 · see citing works
The FGF21–adiponectin axis in controlling energy and vascular homeostasis
Hui, X. H., Feng, T., Liu, Q., Gao, Y., & Xu, A. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw013 · Cited by 102 · see citing works
Taniguchi, H., Tanisawa, K., Sun, X., Kubo, T., & Higuchi, M. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3308 · Cited by 102 · see citing works
Peripherally derived FGF21 promotes remyelination in the central nervous system
Kuroda, M., Muramatsu, R., Maedera, N., Koyama, Y., Hamaguchi, M., Fujimura, H., Yoshida, M., Konishi, M., Itoh, N., Mochizuki, H., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci94337 · Cited by 99 · see citing works
Self-citationFGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation
Keinicke, H., Sun, G., Mentzel, C. M. J., Fredholm, M., John, L. M., Andersen, B., Raun, K., & Gerstenberg, M. K. (2020) · Endocrine Connections · doi:10.1530/ec-20-0152 · Cited by 101 · see citing works
Fibroblast growth factor 21 night watch: advances and uncertainties in the field
Kharitonenkov, A., & DiMarchi, R. D. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12580 · Cited by 97 · see citing works
Yie, J., Wang, W., Deng, L., Tam, L., Stevens, J., Chen, M. M., Li, Y., Xu, J., Lindberg, R., Hecht, R., et al. (2012) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2012.01325.x · Cited by 99 · see citing works
Conversion of a Paracrine Fibroblast Growth Factor into an Endocrine Fibroblast Growth Factor
Goetz, R. M., Ohnishi, M., Kır, S., Kurosu, H., Wang, L., Pastor, J. V., Ma, J., Gai, W., Kuro‐o, M., Razzaque, M. S., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.342980 · Cited by 98 · see citing works
RECENT RESEARCH ON THE GROWTH PLATE: Recent insights into the regulation of the growth plate
Lui, J. C. K., Nilsson, O., & Baron, J. (2014) · Journal of Molecular Endocrinology · doi:10.1530/jme-14-0022 · Cited by 96 · see citing works
Henriksson, E., & Andersen, B. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.601349 · Cited by 95 · see citing works
Emerging role of fibroblast growth factors 15/19 and 21 as metabolic integrators in the liver
Cicione, C., Degirolamo, C., & Moschetta, A. (2012) · Hepatology · doi:10.1002/hep.25929 · Cited by 95 · see citing works
Wu, S., Levenson, A. E., Kharitonenkov, A., & Luca, F. D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.343707 · Cited by 94 · see citing works
The Structural Biology of the FGF19 Subfamily
Beenken, A., & Mohammadi, M. (2012) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4614-0887-1_1 · Cited by 93 · see citing works
FGF21: a novel prospect for the treatment of metabolic diseases.
Kharitonenkov, A., & Shanafelt, A. B. (2009) · PubMed · Cited by 91 · see citing works
Plasma FGF21 Is Elevated by the Intense Lipid Mobilization of Lactation
Schoenberg, K. M., Giesy, S. L., Harvatine, K. J., Waldron, M. R., Cheng, C., Kharitonenkov, A., & Boisclair, Y. R. (2011) · Endocrinology · doi:10.1210/en.2011-1425 · Cited by 90 · see citing works
Fibroblast growth factors, old kids on the new block
Li, X., Wang, C., Xiao, J., McKeehan, W. L., & Wang, F. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.12.014 · Cited by 89 · see citing works
Fibroblast Growth Factor 21 and the Adaptive Response to Nutritional Challenges
Martínez‐Garza, Ú., Torres‐Oteros, D., Yarritu, A., Marrero, P. F., Haro, D., & Relat, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194692 · Cited by 87 · see citing works
- Authors
- Suzuki, M., Uehara, Y., Motomura-Matsuzaka, K., Oki, J., Koyama, Y., Kimura, M., Asada, M., Komi-Kuramochi, A., Oka, S., & Toru, T.
- Affiliations
- National Institute of Advanced Industrial Science and Technology (JP)
- Tokyo University of Science (JP)
- Signaling Molecules Research Laboratory (M.S., Y.U., K.M.-M., J.O., M.K., M.A., A.K.-K., S.O., T.I.), Ibaraki 305-8566, Japan
- ORCID
- Asada, Masahiro
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-04-01
- Volume
- 22
- Issue
- 4
- Pages
- 1006-1014
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- PMC
- PMC5419549
- OpenAlex
- W2110534048
- Cited by
- 345
- References
- 34
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 18 · 2023: 11 · 2022: 18 · 2021: 18 · 2020: 19 · 2019: 19 · 2018: 13 · 2017: 25 · 2016: 26 · 2015: 25 · 2014: 16 · 2013: 20 · 2012: 27
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Physical Sciences › Environmental Science › Water Science and Technology › Fluoride Effects and Removal
- Keywords
- β-Klotho, FGF21, fibroblast growth factor 23, FGFR1c, FGF receptor signaling, target cell specificity, heparan sulfate proteoglycans, adipocytes, insulin-independent glucose transport, Ba/F3 cells, 3T3-L1 adipocytes, phosphate homeostasis, ketogenesis, starvation adaptation
- MeSH terms
- Fibroblast Growth Factor-23, Klotho Proteins, Animals, Fibroblast Growth Factors, Glucuronidase, Protein Binding, RNA, Messenger, Immunoblotting, Signal Transduction, Gene Expression, Reverse Transcriptase Polymerase Chain Reaction, 3T3-L1 Cells, Glucose Transport Proteins, Facilitative, Mice, Receptor, Fibroblast Growth Factor, Type 1, Receptor, Fibroblast Growth Factor, Type 3
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