FGF 21 Rat
Description
Introduction to Fibroblast Growth Factor 21 (FGF21)
Fibroblast Growth Factor 21 (FGF21) is an endocrine hormone primarily secreted by the liver, with critical roles in regulating glucose homeostasis, lipid metabolism, and energy expenditure . In rodent models, FGF21 interacts with β-Klotho and fibroblast growth factor receptors (FGFRs) to mediate systemic metabolic effects, making rats a key species for studying its therapeutic potential in obesity, diabetes, and cardiovascular diseases .
FGF21 in Rat Metabolic Studies
Key findings from rat models include:
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Glucose Regulation: FGF21 enhances insulin sensitivity by suppressing hepatic glucose production and upregulating glucose uptake in adipocytes. In diabetic rats, FGF21 administration reduced blood glucose by 18–25% and improved glucose tolerance .
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Lipid Metabolism: FGF21 lowers serum triglycerides (TG) and non-esterified fatty acids (NEFA) by 30–40% in high-fat diet (HFD) rats through increased lipolysis and fatty acid oxidation .
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Energy Balance: Central FGF21 infusion in obese rats increases energy expenditure by 15–20% without altering body weight, suggesting brain-mediated metabolic effects .
Cardiovascular Effects of FGF21 in Rats
FGF21 exhibits dual cardiovascular actions in rats:
In HFD rats, FGF21 resistance (↓ FGFR2/3 expression) exacerbates cardiovascular dysfunction, which is reversible with recombinant human FGF21 (rhFGF21) therapy .
FGF21 and Dietary Interventions in Rats
Dietary modulation profoundly impacts FGF21 signaling:
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Low-Protein Diets: Increase hepatic Fgf21 mRNA by 20–25-fold and serum FGF21 levels by 3–4× within 4 days .
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High-Fat Diets: Induce FGF21 resistance via downregulation of FGFR2 (↓ 50%) and FGFR3 (↓ 30%) in the liver .
Therapeutic Implications and Pharmacological Studies
Pharmacological agents tested in rats:
Mechanisms of Action in Rodent Models
FGF21 signaling in rats involves:
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Hepatic Pathway: FGF21 binds FGFR1-β-Klotho complexes to suppress gluconeogenic genes (G6pc, Pck1) .
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Central Nervous System: Intracerebroventricular FGF21 activates hypothalamic neurons, increasing adiponectin and insulin sensitivity .
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Cardiac Protection: Autocrine FGF21 in cardiomyocytes reduces oxidative stress via AMPK/SIRT1 pathways .
Table 1: Metabolic Effects of FGF21 in Rat Studies
Table 2: FGF21 Expression Under Dietary Conditions
Product Specs
Product Science Overview
FGF-21 was first identified in 2000 and belongs to the endocrine FGF subfamily, which also includes FGF-19 and FGF-23 . Unlike other FGFs, members of this subfamily lack a heparin-binding domain, allowing them to circulate freely as endocrine factors and diffuse within tissues . FGF-21 is encoded by the FGF-21 gene and is specifically induced by HMGCS2 activity .
FGF-21 is a potent regulator of glucose homeostasis and lipid metabolism. It was originally identified as a hormone that stimulates glucose uptake in adipocytes . Upon fasting, FGF-21 is induced and secreted from the liver, where it acts on adipose tissues to induce metabolic adaptation to fasting . Additionally, FGF-21 has been shown to reduce plasma insulin levels and promote weight loss in animal models .
Recombinant FGF-21 is produced using microbial industrial fermentation, with Escherichia coli being the most commonly used expression system . Advances in genetic engineering have led to the development of high-yield production strains, significantly improving the efficiency of FGF-21 production . The use of double promoter and tandem gene strategies has further enhanced the expression levels of recombinant FGF-21 .
FGF-21 has shown promise in preclinical trials for treating metabolic disorders such as obesity, diabetes, and non-alcoholic fatty liver disease . Its ability to regulate glucose and lipid metabolism makes it a potential therapeutic candidate for these conditions. Additionally, FGF-21’s role in metabolic adaptation to fasting has sparked interest in its potential applications in weight management and metabolic health .
