[Gene of The Week] FGF21: Metabolic Disease Related Gene

The FGF21 gene plays a significant role in the pathogenesis of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In this article, we review the FGF21 gene, a pathogenic gene of metabolic diseases, hoping to give you insights on FGF21 and its role in metabolic disorders.

Background Information – FGF21 Gene

Overview of FGF21 Gene Research

The Fibroblast Growth Factor (FGF) gene family is involved in a wide range of mitogenic and cell survival activities and participates in various biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. Fibroblast growth factor 21 (FGF21) is a liver cytokine - a hormone secreted by the liver through signal transduction via the FGF21 receptor in the paraventricular nucleus of the hypothalamus to regulate the sugar intake and preference for sweets. Secretion of FGF21 is associated with decreased dopamine neurotransmission in the nucleus accumbens. The functions of FGF21 are mainly manifested in glucose metabolism, lipid metabolism, and insulin resistance.

Diseases associated with FGF21 include acquired lipodystrophy and hepatocellular clear cell carcinoma. Its related pathways include:

• Lipoprotein metabolism and electron transport in the respiratory chain.
• ATP produced by chemical permeation coupling.
•  The heat is produced by uncoupling.

Gene ontology (GO) annotations related to this gene include growth factor activity and fibroblast growth factor receptor binding. Stimulates glucose uptake by differentiated adipocytes by inducing the glucose transporter SLC2A1/GLUT1 (instead of SLC2A4/GLUT4). The activity of FGF21 requires the presence of KLB.

Mice lacking FGF21 cannot fully induce PGC-1α expression in response to prolonged fasting, resulting in impaired gluconeogenesis and ketone production. In mice, prolonged fasting of PPAR-α strongly induces FGF21 expression in the liver, which induces the transcriptional coactivator PGC-1α, and stimulates liver gluconeogenesis, fatty acid oxidation, and ketogenesis. PPAR-γ also induces FGF21 expression in white adipose tissue, indicating that it also regulates metabolism in the feeding state. FGF21 is induced in rodents and humans on a low protein diet and reduces dietary methionine levels of the essential amino acid. After a specific knockout of FGF21 in the liver, mice developed fatty liver and hyperlipidemia, reducing serum ketone body levels.

Expression of FGF21 Gene in Human Tissues

Metabolic Disease Models

Animal models of metabolic diseases are important tools for revealing pathophysiology and providing novel insights for the development of new therapies and drugs. Cyagen has developed a series of metabolic disease models, such as obesity, diabetes, atherosclerosis, non-alcoholic fatty liver disease, pancreatitis, etc. to support research. In addition to genetically engineered mouse models, some models simulate human diseases through drug induction and/or diet induction techniques. Researchers may use such models to study the pathogenesis of related diseases, as well as perform drug screening and efficacy evaluations.

>> Learn more about metabolic disease models

You can also find more related mouse models in our selection of research ready Cyagen Knockout Catalog Models.

>> Search for Your Gene of Interest

References:

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2. Talukdar S, Owen BM, Song P, Hernandez G, Zhang Y, Zhou Y, Scott WT, Paratala B, Turner T, Smith A, Bernardo B, Müller CP, Tang H, Mangelsdorf DJ, Goodwin B, Kliewer SA (February 2016). "FGF21 Regulates Sweet and Alcohol Preference". Cell Metabolism. 23 (2): 344–9.

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4. Shimazu T, Hirschey MD, Hua L, Dittenhafer-Reed KE, Schwer B, Lombard DB, Li Y, Bunkenborg J, Alt FW, Denu JM, Jacobson MP, Verdin E (December 2010). "SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production". Cell Metabolism. 12 (6): 654–61.

5. Markan KR, Naber MC, Ameka MK, Anderegg MD, Mangelsdorf DJ, Kliewer SA, Mohammadi M, Potthoff MJ (December 2014). "Circulating FGF21 is liver derived and enhances glucose uptake during refeeding and overfeeding". Diabetes. 63 (12): 4057–63.