FGF19 - Fibroblast Growth Factor 19 | Elisa - Clia - Antibody - Protein

Background:

Fibroblast Growth Factor 19 (FGF19) is a member of the fibroblast growth factor (FGF) family, which plays essential roles in regulating cell growth, differentiation, and metabolism. Bile Acid Synthesis: FGF19 is primarily known for its role in bile acid synthesis and metabolism. It is secreted from the small intestine in response to the activation of nuclear bile acid receptor farnesoid X receptor (FXR) by bile acids. FGF19 then enters the bloodstream and acts on hepatocytes (liver cells) to inhibit the expression of cholesterol 7α-hydroxylase (CYP7A1), a key enzyme in the synthesis of bile acids from cholesterol. This negative feedback loop helps regulate bile acid synthesis and maintain bile acid homeostasis. FGF19 also regulates glucose and lipid metabolism. It has been implicated in the regulation of insulin sensitivity, energy expenditure, and hepatic lipid metabolism. FGF19 signaling in the liver can modulate glucose production, lipid synthesis, and bile acid composition, with potential implications for metabolic diseases such as diabetes and non-alcoholic fatty liver disease (NAFLD).FGF19 is primarily expressed in the ileum, the final segment of the small intestine. Its expression is induced by FXR activation in response to bile acids, as well as by other factors such as nutrient availability and gut microbiota composition.FGF19 signals through a complex composed of fibroblast growth factor receptor 4 (FGFR4) and β-Klotho, a co-receptor that confers specificity to FGF19 signaling. Upon binding to its receptors, FGF19 activates downstream signaling pathways such as the Ras-MAPK and PI3K-Akt pathways, which regulate cellular processes involved in metabolism, growth, and survival.

Protein Structure:

FGF19 is a protein composed of 216 amino acids and has a molecular weight of approximately 25 kDa. Unlike classical FGFs, which have a heparin-binding domain, FGF19 binds to its receptor with the assistance of a co-receptor, β-Klotho. The protein structure includes:

• A core region typical of FGFs that facilitates receptor binding.
• Specific domains essential for interaction with β-Klotho, necessary for its biological activity.

Classification and Subtypes:

FGF19 belongs to the FGF15/19 subfamily, which also includes FGF15 (its murine ortholog) and FGF21. These FGFs are atypical due to their endocrine functions, as opposed to the paracrine actions of other FGFs.

Function and Biological Significance:

• Bile Acid Metabolism: FGF19 is produced in the ileum in response to bile acids and transported to the liver, where it inhibits the enzyme cholesterol 7α-hydroxylase (CYP7A1), reducing bile acid synthesis.
• Glucose and Lipid Metabolism: FGF19 influences carbohydrate and lipid metabolism by enhancing glycogen synthesis and insulin sensitivity while reducing lipogenesis.
• Energy Homeostasis: It plays a role in energy expenditure and has been linked to weight regulation and metabolic syndrome.
• Cell Proliferation and Differentiation: FGF19 is involved in cell growth and differentiation processes, particularly in liver cells.

Interactions:

• FGFR4/β-Klotho Complex: FGF19 exerts its effects through binding to the fibroblast growth factor receptor 4 (FGFR4) in the presence of the co-receptor β-Klotho. This binding activates downstream signaling pathways such as MAPK/ERK, PI3K/Akt, and STAT, leading to its metabolic effects.
• Nuclear Receptors: It indirectly interacts with nuclear receptors like FXR (farnesoid X receptor) in the intestine, which regulates its expression.

Clinical Issues:

• Metabolic Diseases: Abnormal levels of FGF19 are associated with metabolic diseases, including obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD). Therapeutic modulation of FGF19 activity is being explored for treating these conditions.
• Cancer: Elevated FGF19 levels have been observed in certain cancers, such as hepatocellular carcinoma (HCC). FGF19 can promote tumor growth and proliferation, making it a potential target for cancer therapy.
• Cholestasis: FGF19-based therapies are being investigated for treating cholestatic liver diseases due to its role in regulating bile acid synthesis.

Summary:

FGF19 is a critical regulator of bile acid synthesis, glucose and lipid metabolism, and energy homeostasis. It functions through binding to the FGFR4/β-Klotho complex, activating several signaling pathways. Abnormal FGF19 levels are linked to metabolic disorders, cancer, and liver diseases, making it a significant focus of therapeutic research. Understanding FGF19's mechanisms and interactions is crucial for developing treatments for these conditions.