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Gene Review

FGF21  -  fibroblast growth factor 21

Homo sapiens

Synonyms: FGF-21, Fibroblast growth factor 21, UNQ3115/PRO10196
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Disease relevance of FGF21

  • This indicates a dual function of FGF21 that may reflect changes in FGFR isotype during progression of differentiated hepatoma cells [1].
  • These data support the development of FGF-21 for the treatment of diabetes and other metabolic diseases [2].
  • FGF-21 administration also led to significant improvements in lipoprotein profiles, including lowering of low-density lipoprotein cholesterol and raising of high-density lipoprotein cholesterol, beneficial changes in the circulating levels of several cardiovascular risk markers/factors, and the induction of a small but significant weight loss [2].

High impact information on FGF21

  • In islets isolated from diabetic rodents, FGF-21 treatment increased islet insulin content and glucose-induced insulin secretion [3].
  • Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways [3].
  • In conclusion, preservation of beta-cell function and survival by FGF-21 may contribute to the beneficial effects of this protein on glucose homeostasis observed in diabetic animals [3].
  • No effect of FGF-21 was observed on islet cell proliferation [3].
  • Islets and INS-1E cells treated with FGF-21 were partially protected from glucolipotoxicity and cytokine-induced apoptosis [3].

Biological context of FGF21


Anatomical context of FGF21


Associations of FGF21 with chemical compounds

  • Strikingly, treatment of cells with FGF-21 and rosiglitazone in combination leads to a pronounced increase in expression of the GLUT1 glucose transporter and a marked synergy in stimulation of glucose transport [4].

Physical interactions of FGF21


Analytical, diagnostic and therapeutic context of FGF21

  • We showed that similar to FGF1 and FGF2, FGF21 mRNA was upregulated in neoplastic and regenerating liver after partial hepatectomy (PH) and CCl(4) administration [1].
  • In situ hybridization analysis confirmed that in contrast to FGF1 and FGF2, expression of FGF21 mRNA was limited to hepatocytes [1].
  • Short-term treatment of normal or db/db mice with FGF-21 lowered plasma levels of insulin and improved glucose clearance compared with vehicle after oral glucose tolerance testing [3].
  • Immunohistochemistry of pancreata from db/db mice showed a substantial increase in the intensity of insulin staining in islets from FGF-21-treated animals as well as a higher number of islets per pancreas section and of insulin-positive cells per islet compared with control [3].


  1. Forced expression of hepatocyte-specific fibroblast growth factor 21 delays initiation of chemically induced hepatocarcinogenesis. Huang, X., Yu, C., Jin, C., Yang, C., Xie, R., Cao, D., Wang, F., McKeehan, W.L. Mol. Carcinog. (2006) [Pubmed]
  2. The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Kharitonenkov, A., Wroblewski, V.J., Koester, A., Chen, Y.F., Clutinger, C.K., Tigno, X.T., Hansen, B.C., Shanafelt, A.B., Etgen, G.J. Endocrinology (2007) [Pubmed]
  3. Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Wente, W., Efanov, A.M., Brenner, M., Kharitonenkov, A., Köster, A., Sandusky, G.E., Sewing, S., Treinies, I., Zitzer, H., Gromada, J. Diabetes (2006) [Pubmed]
  4. Molecular determinants of FGF-21 activity-synergy and cross-talk with PPARgamma signaling. Moyers, J.S., Shiyanova, T.L., Mehrbod, F., Dunbar, J.D., Noblitt, T.W., Otto, K.A., Reifel-Miller, A., Kharitonenkov, A. J. Cell. Physiol. (2007) [Pubmed]
  5. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. 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. J. Biol. Chem. (2007) [Pubmed]
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