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Frontiers of Medicine

Front Med    2013, Vol. 7 Issue (1) : 25-30     DOI: 10.1007/s11684-013-0244-8
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Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology
Huating Li, Jing Zhang, Weiping Jia()
Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital; Shanghai Diabetes Institute; Shanghai Clinical Center of Diabetes, Shanghai 200233, China
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Abstract

Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family. It actually functions as endocrine hormones but does not regulate cell growth and differentiation. It is demonstrated that FGF21 acts on multiple tissue to coordinate carbohydrate and lipid metabolism, including enhancing insulin sensitivity, decreasing triglyceride concentrations, causing weight loss, ameliorating obesity-associated hyperglycemia and hyperlipidemia. Moreover, FGF21 also plays important roles in some physiological processes, such as fasting and feeding, growth hormone axis and thermogenic function of brown adipose tissue. Clinical relevance of FGF21 in humans is still unclear, and the basis and consequences of increased FGF21 in metabolic disease remain to be determined. Both the pharmacological actions and physiological roles make FGF21 attractive drug candidates for treating metabolic disease, but some questions remain to be answered. This article concentrates on recent advances in our understanding of FGF21.

Keywords FGF21      metabolism      pharmacology      physiology      clinical relevance     
Corresponding Authors: Jia Weiping,Email:wpjia@sjtu.edu.cn   
Issue Date: 05 March 2013
 Cite this article:   
Huating Li,Jing Zhang,Weiping Jia. Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology[J]. Front Med, 2013, 7(1): 25-30.
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http://journal.hep.com.cn/fmd/EN/10.1007/s11684-013-0244-8
http://journal.hep.com.cn/fmd/EN/Y2013/V7/I1/25
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Huating Li
Jing Zhang
Weiping Jia
Pharmaceutical effects
Improve insulin sensitivity
Improve dyslipidemia
Weight loss
Improve hepatic steatosis
Increase energy expenditure
Known adverse effect
Bone loss
Tab.1  Pharmacology and adverse effects of recombinant FGF21
Fig.1  Physiological actions of FGF21. (A) In response to fasting or fibrate drugs, FGF21 expression is induced in the liver by the PPARα/RXR heterodimer, and then causes ketogenesis, gluconeogenesis, and torpor; (B) In response to feeding or thiazolidinedione drugs (TZDs), FGF21 expression is induced by the PPARγ/RXR heterodimer in WAT, where FGF21 acts to stimulate PPARγ activity; (C) FGF21 acts as a negative feedback signal to block GH-stimulated lipolysis in adipocytes. FGF21 inhibits growth as part of its broader role in promoting energy conservation during starvation; (D) FGF21 acts to activate and expand the thermogenic machinery to provide the defense against hypothermia.
Fig.1  Physiological actions of FGF21. (A) In response to fasting or fibrate drugs, FGF21 expression is induced in the liver by the PPARα/RXR heterodimer, and then causes ketogenesis, gluconeogenesis, and torpor; (B) In response to feeding or thiazolidinedione drugs (TZDs), FGF21 expression is induced by the PPARγ/RXR heterodimer in WAT, where FGF21 acts to stimulate PPARγ activity; (C) FGF21 acts as a negative feedback signal to block GH-stimulated lipolysis in adipocytes. FGF21 inhibits growth as part of its broader role in promoting energy conservation during starvation; (D) FGF21 acts to activate and expand the thermogenic machinery to provide the defense against hypothermia.
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