FGF-21

Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family, primarily produced in the liver, and plays a crucial role in inter-organ communication related to metabolism. Researchers primarily study FGF21 for its involvement in various cardiovascular and metabolic diseases, including obesity, type 2 diabetes, and liver disorders. Key findings indicate that FGF21 may regulate metabolic processes and protect against conditions such as ventilator-induced lung injury and iron overload-induced liver damage by modulating specific cellular pathways. Additionally, studies suggest that FGF21 has potential therapeutic applications in managing metabolic dysfunction and related diseases, highlighting its significance in ongoing clinical research. As a result, FGF21 is emerging as a promising biomarker and therapeutic target in the field of metabolic health.

Fibroblast Growth Factor 21 (FGF21) is an endogenous hormone belonging to the FGF19 subfamily, primarily produced in the liver, but also expressed in adipose tissue, thymus, heart, pancreas, and skeletal muscle in mice. It is classified as a growth factor and plays a significant role in inter-organ communication. FGF21 is a pleiotropic hormone involved in various physiological processes, including metabolism, reproduction, and immunity. Researchers have extensively studied its roles in cardiovascular and metabolic diseases, ventilator-induced lung injury, iron overload-induced liver injury, and osteoarthritis. FGF21 acts through several pathways, including the AMPK, SIRT1, and mTOR signaling pathways, and has been shown to regulate autophagy, pyroptosis, and ferroptosis. It interacts with receptors and molecules such as NLRP3, caspase-1, and GSDMD, contributing to its protective effects in various conditions. Pharmacokinetic properties of FGF21 are limited, but native FGF21 is noted for poor pharmacokinetics and biophysical properties, prompting the development of FGF21-based drugs with improved profiles. Clinically, FGF21 is being explored for its therapeutic potential in treating metabolic dysfunction-associated steatotic liver disease and other conditions, although it is not yet widely approved for clinical use. Researchers continue to investigate its efficacy and safety in preclinical and clinical studies.

FGF21 acts primarily through the FGFR1 receptor in conjunction with the co-receptor β-Klotho, activating pathways such as AMPK, SIRT1, and mTOR. This activation leads to biological cascades that regulate metabolic processes, autophagy, and inflammation, contributing to its protective roles in various diseases.

Fibroblast growth factor 21 (FGF21) primarily exerts its effects through the activation of the FGF receptors (FGFRs) in conjunction with the co-receptor β-Klotho, initiating signaling cascades such as the AMPK pathway and the SIRT1-mTOR pathway. These pathways mediate various biological processes, including glucose and lipid metabolism, autophagy, and inflammation, while also inhibiting ferroptosis and pyroptosis in specific contexts. Although significant progress has been made in understanding FGF21's mechanisms, some aspects remain incompletely elucidated, particularly regarding its interactions with gut microbiota and other molecular targets.

Current evidence is limited regarding the long-term effects and safety of FGF21-based therapies in diverse populations, particularly in individuals with varying degrees of metabolic dysfunction and comorbidities. Further research is needed to clarify the mechanisms underlying FGF21's protective roles in different diseases, such as its interaction with the gut microbiota and its effects on cardiovascular health, as well as to resolve contradictory findings related to its role in ferroptosis and autophagy. Additionally, larger randomized controlled trials (RCTs) are necessary to establish the efficacy of FGF21 in clinical settings, particularly in conditions like osteoarthritis and ventilator-induced lung injury.