Fibroblast Growth Factor 21 (FGF-21) is a metabolic hormone predominantly produced in the liver, with additional expression in adipose tissue and the pancreas. The C-terminal region of FGF-21 is crucial for its interaction with the co-receptor β-Klotho, which is essential for FGF-21’s biological activity. Upon binding to β-Klotho and FGFR1c (fibroblast growth factor receptor 1c), FGF-21 initiates signaling pathways involved in regulating glucose uptake, lipid metabolism, insulin sensitivity, and energy expenditure. Due to its unique endocrine function within the FGF family, FGF-21 serves as a key biomarker and therapeutic target in metabolic diseases.
In research settings, human C-terminal FGF-21 is frequently studied to understand its role in metabolic disorders such as obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. Measuring levels of circulating FGF-21—particularly the intact, active form—is essential for evaluating its potential as a diagnostic or prognostic biomarker. In clinical applications, FGF-21 analogs or mimetics are under investigation in clinical trials as potential therapies for metabolic syndrome and liver diseases. Additionally, the C-terminal fragment is often targeted in drug design to improve receptor specificity and therapeutic efficacy while minimizing degradation by proteases such as fibroblast activation protein (FAP), which cleaves the C-terminus and inactivates FGF-21.
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