FGF15

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Fibroblast growth factor 15 is a protein in mouse encoded by the Fgf15 gene.[1] It is a member of the fibroblast growth factor (FGF) family but, like FGF19, FGF21 and FGF23, has endocrine functions. FGF19 is the orthologous protein in humans. They are often referred together as FGF15/19.[2][3]

Identification[edit]

FGF15 was first described in developing mouse brain.[4][5][6] There is no human FGF15.

Structure[edit]

The mouse Fgf15 gene is syntenic with the human FGF19 gene.[7] FGF15 and FGF19 proteins share about 50% amino acid identity, are found in the same tissues, and have similar functions in mouse and humans.

Functions[edit]

FGF15 is found in the absorptive cells of the mouse ileum and plays an important role in feedback inhibition of hepatic bile acid synthesis.[8] FGF15 (and FGF19 in humans) function as hormones produced in response to bile acid absorption acting on the farnesoid X receptor FXR, are secreted into the portal venous circulation and bind onto the liver membrane receptor FGFR4/β-Klotho and repress bile acid synthesis by the Cyp7a1 gene.

In a mouse model of chronic diarrhea due to bile acid malabsorption, FGF15 administration, or stimulation of its production, reduced the bile acid loss by inhibiting new synthesis.[9]

FGF15 has effects on energy homeostasis. Fgf15-knock-out mice have reduced liver glycogen storage and are glucose-intolerant.[10]

FGF15 has been implicated in liver regeneration and repair.[11] Fgf15-deficient mice have impaired regeneration.[12]

References[edit]

  1. ^ NCBI. "Mouse FGF15 fibroblast growth factor 15". 
  2. ^ Jones, SA (2012). "Physiology of FGF15/19". Advances in experimental medicine and biology. Advances in Experimental Medicine and Biology 728: 171–82. doi:10.1007/978-1-4614-0887-1_11. ISBN 9781461408871. PMID 22396169. 
  3. ^ Potthoff, M. J.; Kliewer, S. A.; Mangelsdorf, D. J. (2012). "Endocrine fibroblast growth factors 15/19 and 21: from feast to famine". Genes & Development 26 (4): 312–324. doi:10.1101/gad.184788.111. PMC 3289879. PMID 22302876. 
  4. ^ McWhirter, JR; Goulding, M; Weiner, JA; Chun, J; Murre, C (1997). "A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1". Development 124 (17): 3221–32. PMID 9310317. 
  5. ^ Gimeno, L; Hashemi, R; Brûlet, P; Martínez, S (2002). "Analysis of Fgf15 expression pattern in the mouse neural tube". Brain Research Bulletin 57 (3–4): 297–9. doi:10.1016/S0361-9230(01)00717-1. PMID 11922976. 
  6. ^ Gimeno, L; Brûlet, P; Martínez, S (2003). "Study of Fgf15 gene expression in developing mouse brain". Gene expression patterns : GEP 3 (4): 473–81. doi:10.1016/S1567-133X(03)00059-0. PMID 12915315. 
  7. ^ Wright, TJ; Ladher, R; McWhirter, J; Murre, C; Schoenwolf, GC; Mansour, SL (2004). "Mouse FGF15 is the ortholog of human and chick FGF19, but is not uniquely required for otic induction". Developmental biology 269 (1): 264–75. doi:10.1016/j.ydbio.2004.02.003. PMID 15081372. 
  8. ^ Inagaki, T; Choi, M; Moschetta, A; Peng, L; Cummins, CL; McDonald, JG; Luo, G; Jones, SA; Goodwin, B; Richardson, JA; Gerard, RD; Repa, JJ; Mangelsdorf, DJ; Kliewer, SA (2005). "Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis". Cell metabolism 2 (4): 217–25. doi:10.1016/j.cmet.2005.09.001. PMID 16213224. 
  9. ^ Jung D, Inagaki T, Gerard RD, Dawson PA, Kliewer SA, Mangelsdorf DJ, Moschetta A (December 2007). "FXR agonists and FGF15 reduce fecal bile acid excretion in a mouse model of bile acid malabsorption". J. Lipid Res. 48 (12): 2693–700. doi:10.1194/jlr.M700351-JLR200. PMID 17823457. 
  10. ^ Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K, Xu HE, Shulman GI, Kliewer SA, Mangelsdorf DJ (March 2011). "FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis". Science 331 (6024): 1621–4. doi:10.1126/science.1198363. PMC 3076083. PMID 21436455. 
  11. ^ Zhang L, Wang YD, Chen WD, Wang X, Lou G, Liu N, Lin M, Forman BM, Huang W (December 2012). "Promotion of liver regeneration/repair by farnesoid X receptor in both liver and intestine in mice". Hepatology 56 (6): 2336–43. doi:10.1002/hep.25905. PMC 3477501. PMID 22711662. 
  12. ^ Kong B, Huang J, Zhu Y, Li G, Williams J, Shen S, Aleksunes LM, Richardson JR, Apte U, Rudnick DA, Guo GL (May 2014). "Fibroblast growth factor 15 deficiency impairs liver regeneration in mice". Am. J. Physiol. Gastrointest. Liver Physiol. 306 (10): G893–902. doi:10.1152/ajpgi.00337.2013. PMID 24699334.