FGF-21: A Pleiotropic Hormone from Energy Metabolism Regulation to Multi-Organ Protection

Author: Senior Product Manager of UA Views：41

This article systematically elaborates on the molecular characteristics and biological functions of fibroblast growth factor 21 (FGF-21), highlighting its multifaceted role as a core regulator of energy homeostasis in the liver, skeletal muscle, pancreas, and heart. It analyzes the mechanisms by which FGF-21 exerts metabolic regulation through promoting glucose utilization, fatty acid oxidation, and anti-inflammatory signaling pathways.

Recent Advances
Product Information

Recent Advances

FGF-21: A Pleiotropic Hormone from Energy Metabolism Regulation to Multi-Organ Protection

Overview
This article systematically elaborates on the molecular characteristics and biological functions of Fibroblast Growth Factor 21 (FGF-21), highlighting its multifaceted role as a core regulator of energy homeostasis in the liver, skeletal muscle, pancreas, and heart. It analyzes the mechanisms through which FGF-21 exerts metabolic regulation by promoting glucose utilization, fatty acid oxidation, and anti-inflammatory signaling pathways.

I. Molecular Characteristics and Tissue Sources of FGF-21

Fibroblast Growth Factor 21 (FGF-21) is a unique member of the FGF family, functioning as a hormone-like cytokine through endocrine mechanisms. The human FGF-21 gene is located on chromosome 19q13.33, encoding a mature protein composed of 181 amino acid residues with a molecular weight of approximately 22 kDa, including an N-terminal signal peptide sequence and a C-terminal β-klotho binding domain. The primary synthesis site of FGF-21 is the liver, where hepatocytes are the main source of circulating FGF-21. Additionally, FGF-21 is expressed in organs such as skeletal muscle, pancreas, adipose tissue, and heart. In skeletal muscle, FGF-21 protein expression in C2C12 myocytes is induced by insulin, and FGF-21 mRNA in young healthy males is positively regulated by hyperinsulinemia. This suggests that under stress conditions, skeletal muscle can serve as a secretory source of FGF-21, facilitating metabolic communication with adipose tissue.

II. Receptor Binding and Signal Transduction Mechanisms of FGF-21

The signaling of FGF-21 depends on the formation of a stable ternary complex with the effector protein β-klotho (a single-pass transmembrane protein) and FGFR1c (Fibroblast Growth Factor Receptor 1c). In this process, the C-terminus of FGF-21 first binds to β-klotho, followed by its N-terminus specifically binding to FGFR1c, inducing receptor dimerization and activation of downstream signaling pathways. Due to the predominant expression of β-klotho in metabolically active tissues (liver, adipose tissue, pancreas, etc.), FGF-21 signaling exhibits tissue specificity.

III. Metabolic Regulatory Functions of FGF-21

FGF-21 is a major regulator of energy homeostasis, playing a critical role in glucose and lipid metabolism. In glucose metabolism, FGF-21 activates downstream Akt and MAPK signaling pathways, promoting the translocation of glucose transporters in adipocytes and skeletal muscle cells, thereby enhancing peripheral tissue glucose uptake and utilization while improving insulin sensitivity. In lipid metabolism, mice overexpressing FGF-21 exhibit resistance to diet-induced obesity, a mechanism involving the promotion of fatty acid β-oxidation, reduction of lipogenesis, and regulation of cholesterol balance. FGF-21 stimulates lipolysis and fatty acid release in adipose tissue while enhancing fatty acid oxidation and breakdown in the liver.

IV. Anti-Inflammatory and Tissue Protective Effects of FGF-21

Recent studies have revealed the anti-inflammatory and protective roles of FGF-21 in multiple organs. In the liver, FGF-21 suppresses the JNK and NF-κB signaling pathways, mitigating inflammatory responses and reducing hepatic lipid accumulation. In the pancreas, FGF-21 protects pancreatic β-cells from oxidative stress and cytokine-induced damage. In the heart and skeletal muscle, the reduction of JNK and NF-κB signaling pathways is considered a potential mechanism underlying the anti-inflammatory effects of FGF-21.

V. Challenges in Drug Development and Improvement Strategies for FGF-21

The natural FGF-21 has an extremely short in vivo half-life, being rapidly filtered by the glomeruli and susceptible to proteolytic cleavage, severely limiting its clinical translation. Several pharmaceutical companies have employed strategies such as polyethylene glycol (PEG) modification, Fc fusion proteins, or CovX-Body covalent conjugation to extend the half-life of FGF-21. Multiple long-acting FGF-21 proteins have entered clinical research. Clinical studies indicate that long-acting FGF-21 proteins exhibit positive therapeutic effects in alleviating hepatic steatosis in non-alcoholic fatty liver disease patients, reducing body weight, and regulating blood lipids. However, they have not yet demonstrated significant advantages over existing antidiabetic drugs in glycemic control for diabetic patients.

VI. Conclusion

As a unique endocrine-acting member of the FGF family, FGF-21 has emerged as a highly promising therapeutic target in the field of metabolic diseases due to its multifaceted functions in promoting glucose and lipid metabolism, maintaining energy homeostasis, and mediating anti-inflammatory signaling. Although the drug development of its natural form faces challenges, the continuous advancement of long-acting modification strategies has opened broad prospects for clinical applications. Human recombinant FGF-21 protein, as a crucial tool for basic research and drug development, will continue to provide essential support for in-depth exploration of the FGF-21 signaling network and optimization of metabolic disease treatment strategies.

In FGF-21-related basic research and drug screening, high-quality human recombinant FGF-21 protein is a core tool for signaling pathway analysis, cellular functional studies, and pharmacological evaluation. To meet this research demand, UniLove offers FGF-21 Protein, Human, suitable for applications such as FGF-21/β-klotho/FGFR1c binding activity analysis, glucose and lipid metabolism studies in adipocytes and hepatocytes, and in vitro activity evaluation of long-acting FGF-21 analogs.

This article is reviewed and published by the technical expert team of UA

Disclaimer: This article partially utilizes artificial intelligence assistance in its creation. If any content involves copyright or intellectual property issues, please let us know and we promise to verify and remove it as soon as possible.

Purchase recombinant protein, choose Nanjing UA-Bio

UA protein focuses on providing various protein reagents, raw materials, and services required for drug research and development, cell therapy, gene therapy, and basic scientific research, including drug target proteins, immune checkpoint proteins, cytokines, tool enzymes, customized protein expression, and full-length transmembrane protein development. Youai is committed to providing customers with high-quality products and professional services, and building a High-tech Biological Enterprise with International Competitiveness.

Buy antibodiesFind UA www.ua-bio.com | 15 years of protein development experience

Nanjing UA Biotechnology Co., Ltd. Email：order@ua-bio.com Phone：+86-25-56221161

more products

Product Information

The Last The Next