Fibroblast growth factor 19 (FGF19) is a secreted protein which belongs to the FGFs family. FGF19 is expressed in fetal brain, cartilage, retina, and adult gall bladder. FGFs modulate cellular activity via at least 5 distinct subfamilies of high-affinity FGF receptors (FGFRs): FGFR-1, -2, -3, and -4, all with intrinsic tyrosine kinase activity. FGFRs can be important for regulation of glucose and lipid homeostasis. FGF19 has important roles as a hormone produced in the ileum in response to bile acid absorption. It has been shown to cause resistance to diet-induced obesity and insulin desensitization and to improve insulin, glucose, and lipid profiles in diabetic rodents. FGF19 can be considered as a regulator of energy expenditure.
FGF acidic; also known as ECGF; FGF-1and HBGF-1; is a non-glycosylated heparin binding growth factor that is expressed in the brain; kidney; retina; smooth muscle cells; bone matrix; osteoblasts; astrocytes and endothelial cells. It is a mitogenic peptide that is produced by multiple cell types and stimulates the proliferation of cells of mesodermal; ectodermal; and endodermal origin. Its association with heparan sulfate is a prerequisite for activation of FGF receptors. Internalized FGF acidic migrates to the nucleus where it is phosphorylated by nuclear PKC delta; exported to the cytosol; dephosphorylated; and degraded. Intracellular FGF acidic inhibits p53 activity and proapoptotic signaling.
Fibroblast growth factor 20 (FGF-20) is a member of the FGF gene family, which currently contains 22 members. Based on its structure, it is further classified as an FGF-9 subfamily member. All FGF family members are heparin-binding growth factors with a 120 amino acid (aa) core FGF domain that exhibits a beta -trefoil structure. The cDNA of FGF-20 predicts a 211 aa polypeptide without a canonical signal peptide sequence, a feature shared with other members of this subfamily. Nevertheless, it is secreted with a molecular weight of 27 kDa. FGF-20 is known to bind to heparin. No alternate splice forms have been reported. However, three amino acid polymorphisms are known, and single nucleotide polymorphisms in noncoding regions that may effect expression show a strong correlation with a risk of developing Parkinson’s disease. Human FGF-20 shows 98% aa identity to bovine FGF-20 and 95% aa identity to both rat and mouse FGF-20. Within the FGF-9 subfamily, FGF-20 is 69% and 63% aa identical to human FGF-9 and FGF-16, respectively. Human FGF-20 is reported to be promiscuous in its selection of receptors which include FGF R1c, FGF R2c, FGF R3b, FGF R3c and FGF R4. FGF-20 is expressed a variety of cells, including dopaminergic neurons, fibroblasts, keratinocytes and breast epithelium, and multiple sites in the fetus. Finally, the expression of FGF-20 and DKK-1 is regulated by beta -catenin during development and tumorigenesis, implying that FGF-20 may play a role in the oncogenesis induced by the Wnt signaling pathway.
Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regulates systemic glucose homeostasis and insulin sensitivity.
Fibroblast Growth Factor 21 (FGF21) is a growth factor that belongs to the FGF family. FGF family proteins play a central role during prenatal development and postnatal growth and regeneration of mamy tissues, by promoting cellular proliferation and differentiation. FGF21 is a potent activator of glucose uptake on adipocytes, protects animal from diet-induced obesity when overexpression in transgenic mice, and lower blood glucose and triglyceride levels when therapeutically adiministered to diabetic redents. FGF21 is produced by hepatocytes in reponse to free fatty acid stimulation of a PPARa/RXR dimeric complex. This situation occurs clinically during starvation, or following the ingestionof a highly-fat/low-carbohydrate diet.Upon FGF21 secretion, white adipose tissue is induced to release free fatty acids from triglyceride stores. Once free fatty acid reach hepatocytes, they are oxidized and reduced to acetyl-CoA. The acetyl-CoA is recombined into 4-carbon ketone bodies, release, and transported to peripheral tissue for TCA processing and energy generation.
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