FGF-21

Fibroblast growth factor 21 (FGF21) is a non-canonical fibroblast growth factor primarily produced in the liver, with additional expression in adipose tissue, heart, and pancreas. Researchers primarily study FGF21 for its role in metabolic regulation and its potential implications in cardiovascular and metabolic diseases. Key findings indicate that FGF21 is involved in correcting metabolic dysfunction, influencing energy balance, and regulating lipid metabolism, particularly in relation to atherosclerosis and obesity. Current research highlights FGF21's multifaceted roles in various physiological processes and its potential as a biomarker and therapeutic target in metabolic disorders. Clinical evidence indicates that FGF21-based therapies may offer promising strategies for addressing conditions associated with metabolic dysfunction.

Fibroblast Growth Factor 21 (FGF21) is an endogenous hormone belonging to the fibroblast growth factor family, specifically the FGF19 subfamily. It is primarily produced in the liver, but is also expressed in adipose tissue, thymus, heart, pancreas, and skeletal muscle. FGF21 is a non-canonical growth factor that functions as an endocrine hormone, playing a critical role in inter-organ communication. Researchers have observed that FGF21 is involved in various physiological processes, including metabolism, reproduction, and immunity. It has gained significant attention for its potential therapeutic applications in correcting metabolic dysfunctions, such as those seen in diabetes and obesity. Additionally, FGF21 has been implicated in cardiovascular and metabolic diseases, osteoarthritis, and even as a potential biomarker for various conditions. The mechanism of action of FGF21 involves its interaction with specific receptors and pathways, including the SIRT1-mTOR signaling pathway, which mediates autophagy and other cellular processes. FGF21 also influences pathways related to adenosine 5'-monophosphate-activated protein kinase and silent information regulator 1. Pharmacokinetic properties of FGF21 are characterized by poor bioavailability and suboptimal pharmacokinetics, which have prompted the development of FGF21-based drugs with improved properties. Researchers have found that these new generations of drugs hold promise for clinical translation. Currently, FGF21-based therapies are being explored for their potential in treating metabolic dysfunction-associated steatotic liver disease and other conditions. However, the regulatory standing and clinical use of FGF21 are still under investigation, with ongoing preclinical and clinical studies aimed at establishing its efficacy and safety.

FGF21 acts on the FGF receptor complex, requiring the co-receptor β-Klotho for its activity. This interaction triggers downstream signaling pathways such as the SIRT1-mTOR and AMPK pathways, leading to effects on metabolism, autophagy, and cellular stress responses.

Fibroblast growth factor 21 (FGF21) primarily signals through the FGF receptor 1 (FGFR1) in complex with β-klotho, activating downstream pathways such as AMP-activated protein kinase (AMPK) and the SIRT1-mTOR signaling pathway. This signaling cascade regulates glucose and lipid metabolism, promotes energy expenditure, and enhances autophagy, contributing to the alleviation of metabolic dysfunctions and inflammation. While the full spectrum of FGF21's mechanisms, including its interaction with microRNA-33 and effects on macrophage actions, remains to be fully elucidated, its role in inter-organ crosstalk and various physiological processes is well established.

Current evidence is limited regarding the precise mechanisms through which FGF21 regulates lipid metabolism and its interactions with microRNAs, particularly miR-33, in macrophages and their implications for atherosclerosis. Further research is needed to clarify the pharmacokinetics and biophysical properties of FGF21-based therapies, as well as to conduct larger randomized controlled trials (RCTs) that assess the long-term effects of FGF21 interventions across diverse populations, including those with varying metabolic conditions. Additionally, the role of FGF21 in the context of osteoarthritis and its potential as a therapeutic agent requires further exploration, particularly in human studies that validate findings from animal models.