FGF21

Fibroblast Growth Factor 21 (FGF21) is a protein that in humans is encoded by the FGF21 gene. FGF21 is a member of the fibroblast growth factor (FGF) family, which is involved in a variety of biological processes including cell growth, embryonic development, and metabolism. FGF21 specifically has been identified as a potent metabolic regulator, playing a significant role in the regulation of glucose homeostasis, lipid metabolism, and insulin sensitivity.

FGF21 exerts its effects by binding to a complex of FGF receptors (FGFRs) and a co-receptor, β-Klotho, which is predominantly expressed in the liver, adipose tissue, and pancreas. The activation of this receptor complex leads to the initiation of signaling pathways that promote insulin sensitivity, enhance glucose uptake, and facilitate lipid oxidation, thereby contributing to improved metabolic outcomes.

Research has shown that FGF21 is induced in the liver in response to metabolic stress, such as prolonged fasting or ketogenic diets, and plays a key role in the adaptation to fasting by promoting gluconeogenesis, ketogenesis, and energy expenditure. Additionally, FGF21 has been implicated in the regulation of body weight and appetite, mediated through its action on the central nervous system, particularly the hypothalamus.

Given its broad metabolic effects, FGF21 has attracted significant interest as a potential therapeutic target for the treatment of metabolic syndrome, obesity, type 2 diabetes, and other metabolic disorders. Several synthetic FGF21 analogs and mimetics are currently under development and clinical investigation, showing promise in improving metabolic parameters in preclinical and early clinical studies.

However, the physiological and pharmacological complexities of FGF21, including its tissue-specific actions and the regulation of its activity, remain areas of active research. Understanding the precise mechanisms by which FGF21 modulates metabolic processes is crucial for the development of effective FGF21-based therapies.