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Exp Clin Endocrinol Diabetes 2020; 128(11): 752-770
DOI: 10.1055/a-0879-2968
Review

Circulating FGF21 Levels in Human Health and Metabolic Disease

Michaela Keuper   *
1   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Tübingen, Germany
2   German Center for Diabetes Research (DZD), Neuherberg, Germany
3   Department of Molecular Bioscience, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
,
Hans-Ulrich Häring
1   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Tübingen, Germany
2   German Center for Diabetes Research (DZD), Neuherberg, Germany
4   Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany
5   Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
,
Harald Staiger
1   Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Tübingen, Germany
2   German Center for Diabetes Research (DZD), Neuherberg, Germany
4   Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany
6   Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls University Tübingen, Tübingen, Germany
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Abstract

Human fibroblast growth factor 21 (FGF21) is primarily produced and secreted by the liver as a hepatokine. This hormone circulates to its target tissues (e. g., brain, adipose tissue), which requires two components, one of the preferred FGF receptor isoforms (FGFR1c and FGFR3c) and the co-factor beta-Klotho (KLB) to trigger downstream signaling pathways. Although targeting FGF21 signaling in humans by analogues and receptor agonists results in beneficial effects, e. g., improvements in plasma lipids and decreased body weight, it failed to recapitulate the improvements in glucose handling shown for many mouse models. FGF21’s role and metabolic effects in mice and its therapeutic potential have extensively been reviewed elsewhere. In this review we focus on circulating FGF21 levels in humans and their associations with disease and clinical parameters, focusing primarily on obesity and obesity-associated diseases such as type-2 diabetes. We provide a comprehensive overview on human circulating FGF21 levels under normal physiology and metabolic disease. We discuss the emerging field of inactivating FGF21 in human blood by fibroblast activation protein (FAP) and its potential clinical implications.

Key words:

hepatokine - metabolic disease - obesity - diabetes

* Current address: Department of Molecular Biosciences, The Wenner- Gren Institute, Stockholm University, 106 91 Stockholm, Sweden, email: michaela.keuper@su.se




Publication History

Received: 03 December 2018
Received: 13 March 2019

Accepted: 18 March 2019

Article published online:
20 May 2019

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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