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fibroblast growth factor 21; FGF-21 (FGF21)

Function: - stimulates glucose uptake in differentiated adipocytes via induction of glucose transporter SLC2A1/GLUT1 expression - does not induce SLC2A4/GLUT4 expression - activity requires presence of KLB (coreceptor) [6] - interacts (via C-terminus) with KLB (beta-klotho) [6] - interacts with FGFR4 - functions in thymus, in production of T-cells [5] Structure: - belongs to the heparin-binding growth factors family Compartment: secreted (putative) Expression: - expressed by the liver in mice - expressed by thymic epithelial cells Comparative biology: - secreted by the liver in response to starvation in mice - inhibition of histone deacetylase 3 stimulates expression of FGF-21 in mice [4] - increases insulin sensitivity in mice - inhibits IGF-1 in mice - stimulates ketone body production in mammals - transgenic mice overexpressing of FGF21 show increased mean life span in mice (30% males, 40% females) without reducing food intake - maximum life span also likely increased [3] - overexpression of FGF21 in mice prevents thymic lipoatrophy [5] - FGF21 inhibits alcohol drinking by acting on the brain - beta-klotho is a coreceptor for FGF21 & defects increase appetite of mice for alcohol Pathology: - high plasma FGF21 found in patients with type 2 diabetes Laboratory: - serum FGF21 may be biomarker for risk of type 2 diabetes

General

fibroblast growth factor

Properties

SIZE: entity length = 209 aa MW = 22 kD COMPARTMENT: extracellular compartment MOTIF: signal sequence {1-28} SECRETED-BY: endothelial cell

Database Correlations

OMIM 609436 UniProt Q9NSA1 Pfam PF00167 Entrez Gene 26291 Kegg hsa:26291

References

  1. UniProt :accession Q9NSA1
  2. NIEHS-SNPs http://egp.gs.washington.edu/data/fgf21/
  3. Mangelsdorf D, Zhang Y, Kliewer S The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. elife. 2012;1:e00065. Epub 2012 Oct 15. PMID: 23066506
  4. Li H et al Sodium butyrate stimulates expression of fibroblast growth factor 21 in liver by inhibition of histone deacetylase 3. Diabetes. 2012 Apr;61(4):797-806. Epub 2012 Feb 14. PMID: 22338096
  5. Xiong A Researchers awarded $10.5 million to study anti-aging hormone. Yale News. Oct 4, 2016 http://yaledailynews.com/blog/2016/10/04/researchers-awarded-10-5-million-to-study-anti-aging-hormone/
  6. Schumann G, Liu C, O'Reilly P et al. KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference. Proc Natl Acad Sci U S A 2016 Dec 13; 113:14372. PMID: 27911795