FGF 21 Human
Greater than 96.0% as determined by:
(a) Analysis by RP-HPLC.
(b) Analysis by SDS-PAGE.
Description
Fibroblast Growth Factor -21 Human Recombinant produced in E.Coli is a single, non-glycosylated, polypeptide chain containing 181 amino acids, having a molecular weight of 19.4 kDa.
The FGF-21 is purified by proprietary chromatographic techniques.
Product Specs
The FGF family comprises over 20 small (~17–26 kDa) secreted peptides. Initial research on these proteins centered around their capacity to promote fibroblast proliferation, a mitogenic effect mediated by fibroblast growth factor receptors (FGFRs) 1, 2, or 3. A fourth related tyrosine kinase receptor (FGFR4) exhibited FGF binding capabilities but did not trigger a mitogenic response.
FGFs exert their effects on cellular activity through at least five distinct subfamilies of high-affinity FGFRs: FGFR-1, -2, -3, and -4, each possessing intrinsic tyrosine kinase activity and, with the exception of FGFR-4, multiple splice isoforms, and FGFR-5, which lacks an intracellular kinase domain. Evidence suggests that FGFRs may play a significant role in regulating glucose and lipid homeostasis. Mice exhibiting overexpression of a dominant negative form of FGFR-1 develop diabetes, implying that proper FGF signaling is crucial for normal cell function and maintaining glycemic control. FGFR-2 appears to be a key player in pancreatic development. Furthermore, FGFR-4 has been linked to cholesterol metabolism and bile acid synthesis.
FGF-19 has demonstrated the ability to induce resistance to diet-induced obesity and improve glucose and lipid profiles in diabetic rodents, along with desensitization. Given that these effects are at least partially mediated by observed changes in metabolic rates, FGF-19 can be considered a regulator of energy expenditure.
Although FGF-21 is primarily expressed in the liver, a comprehensive understanding of its bioactivity and mechanism of action remains elusive. FGF-21 is a potent stimulator of glucose uptake in adipocytes, offers protection against diet-induced obesity in transgenic mice overexpressing the protein, and reduces blood glucose and triglyceride levels when administered therapeutically to diabetic rodents.
Recombinant Human Fibroblast Growth Factor -21, produced in E. coli, is a single, non-glycosylated polypeptide chain comprising 181 amino acids with a molecular weight of 19.4 kDa.
Purification of FGF-21 is achieved using proprietary chromatographic methods.
For long-term storage, adding a carrier protein (0.1% HSA or BSA) is recommended.
Avoid repeated freeze-thaw cycles.
Purity exceeds 96.0% as determined by:
(a) Reverse-phase high-performance liquid chromatography (RP-HPLC) analysis.
(b) Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis.
The half-maximal effective concentration (ED50), determined using a thymidine uptake assay with BaF3 cells transfected with FGF receptors, is less than 0.5 µg/ml. This corresponds to a specific activity greater than 2.0 × 103 IU/mg in the presence of 5 µg/ml recombinant MuKlotho-β and 10 µg/ml heparin.
HPIPDS SPLLQFGGQV RQRYLYTDDA QQTEAHLEIR EDGTVGGAAD QSPESLLQLK ALKPGVIQIL GVKTSRFLCQ RPDGALYGSL HFDPEACSFR ELLLEDGYNV YQSEAHGLPL HLPGNKSPHR DPAPRGPARF LPLPGLPPAP PEPPGILAPQ PPDVGSSDPL SMVGPSQGRS PSYAS.
Product Science Overview
FGF21 is a protein consisting of 209 amino acids, with a signal peptide of 28 amino acids at the N-terminus, resulting in a mature FGF21 polypeptide of 181 amino acids . The protein also contains a disulfide bond (Cys75-Cys93) within its core domain, which contributes to its stability .
FGF21 is expressed in various tissues, including the liver, adipose tissue, and pancreas. It is secreted into the bloodstream, where it acts on distant target tissues, making it an endocrine hormone .
FGF21 has been extensively studied for its role in metabolic regulation. It has several key functions:
- Glucose Homeostasis: FGF21 enhances glucose uptake in peripheral tissues, thereby improving insulin sensitivity and reducing blood glucose levels .
- Lipid Metabolism: It promotes the oxidation of fatty acids and reduces lipid accumulation in the liver, which can help prevent conditions like fatty liver disease .
- Energy Expenditure: FGF21 increases energy expenditure by stimulating thermogenesis in brown adipose tissue .
- Anti-inflammatory Effects: It has been shown to reduce inflammation, which is beneficial in conditions like obesity and type 2 diabetes .
Recombinant human FGF21 (rhFGF21) has been developed to harness its therapeutic potential. It has shown promise in treating various metabolic disorders, including:
- Type 2 Diabetes: rhFGF21 improves insulin sensitivity and glycemic control in diabetic patients .
- Obesity: It aids in weight loss by enhancing lipid metabolism and energy expenditure .
- Cardiovascular Diseases: FGF21’s anti-inflammatory properties can help reduce the risk of cardiovascular complications associated with metabolic disorders .
Producing rhFGF21 in a biologically active form poses several challenges. When expressed in bacterial systems, rhFGF21 tends to form inclusion bodies, making the purification process labor-intensive and time-consuming . Researchers have developed various strategies to improve the soluble expression and secretion of rhFGF21, such as optimizing codon usage and using specific signal peptides .
The potential of FGF21 as a therapeutic agent continues to be explored. Ongoing research aims to better understand its mechanisms of action and develop more efficient production methods. Additionally, clinical trials are being conducted to evaluate the efficacy and safety of rhFGF21 in treating a broader range of metabolic and inflammatory diseases.
In conclusion, Fibroblast Growth Factor-21 (Human Recombinant) represents a promising avenue for the treatment of metabolic disorders. Its multifaceted roles in glucose and lipid metabolism, energy expenditure, and inflammation make it a valuable target for therapeutic intervention.
