The FGF family comprises over 20 small (~17-26 kDa) secreted peptides, initially known for stimulating fibroblast proliferation. This mitogenic activity is mediated by FGF receptors (FGFRs) 1, 2, or 3. A fourth receptor, FGFR4, binds FGFs but doesn't induce a mitogenic response.
FGFs regulate cellular activity through at least five high-affinity FGFR subfamilies: FGFRs 1-4, possessing intrinsic tyrosine kinase activity (with multiple splice isoforms except FGFR4), and FGFR-5, lacking an intracellular kinase domain. Evidence suggests FGFRs' importance in glucose and lipid homeostasis regulation. Overexpressing a dominant-negative FGFR-1 form in pancreatic beta cells causes diabetes in mice, implying that proper FGF signaling is crucial for normal beta cell function and blood sugar control. FGFR-2 appears critical during pancreatic development, while FGFR-4 is implicated in cholesterol metabolism and bile acid synthesis.
FGF-19 confers resistance to diet-induced obesity and insulin desensitization, improving insulin, glucose, and lipid profiles in diabetic rodents. These effects, partly mediated by metabolic rate changes, position FGF-19 as an energy expenditure regulator.
Although primarily expressed in the liver, FGF-21's bioactivity and action mechanism were unclear until recently. FGF-21 potently activates glucose uptake in adipocytes, protects against diet-induced obesity when overexpressed in transgenic mice, and reduces blood glucose and triglyceride levels when administered therapeutically to diabetic rodents.
Reconstitute the lyophilized FGF-19 in sterile 1X PBS at a concentration of at least 100µg/ml. This solution can be further diluted in other aqueous solutions.
FGF19 is a protein encoded by the FGF19 gene. It is primarily expressed in the ileum, a part of the small intestine, and is involved in regulating bile acid synthesis in the liver. FGF19 achieves this by binding to FGFR4 and β-Klotho, which leads to the activation of downstream signaling pathways, including the MAPK and PI3K-Akt pathways .
FGF19 has significant effects on carbohydrate, lipid, and bile acid metabolism. It inhibits bile acid synthesis by downregulating the enzyme cholesterol 7α-hydroxylase (CYP7A1), which is the rate-limiting step in bile acid production. Additionally, FGF19 influences glucose metabolism by enhancing glycogen synthesis and reducing gluconeogenesis in the liver .
Due to its regulatory effects on metabolism, FGF19 has been studied for its potential therapeutic applications in metabolic disorders such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. Recombinant FGF19 has shown promise in preclinical studies for improving insulin sensitivity and reducing liver fat .
Interestingly, FGF19 has also been implicated in cancer, particularly hepatocellular carcinoma (HCC). Overexpression of FGF19 has been associated with tumor progression and poor prognosis in HCC patients. Studies have shown that FGF19 can promote cell proliferation, invasion, and inhibit apoptosis in HCC cells. This makes FGF19 a potential target for therapeutic intervention in HCC .
Recombinant FGF19 is produced using recombinant DNA technology, which involves inserting the FGF19 gene into a suitable expression system, such as bacteria or mammalian cells, to produce the protein in large quantities. This recombinant form of FGF19 is used in various research studies to understand its biological functions and therapeutic potential .