Brown Adipose Tissue Responds to Cold and Adrenergic Stimulation by Induction of FGF21

Dionysius V Chartoumpekis,Panos G Ziros,Ioannis G Habeos,Agathoklis I Psyrogiannis,Venetsana E Kyriazopoulou,Athanasios G Papavassiliou

doi:10.2119/molmed.2011.00075

Dionysius V Chartoumpekis, Panos G Ziros + Show 4 more

Open Access

https://doi.org/10.2119/molmed.2011.00075

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Abstract

Fibroblast growth factor-21 (FGF21) is a pleiotropic protein involved in glucose, lipid metabolism and energy homeostasis, with main tissues of expression being the liver and adipose tissue. Brown adipose tissue (BAT) is responsible for cold-induced thermogenesis in rodents. The role of FGF21 in BAT biology has not been investigated. In the present study, wild-type C57BL/6J mice as well as a brown adipocyte cell line were used to explore the potential role of cold exposure and β3-adrenergic stimulation in the expression of FGF21 in BAT. Our results demonstrate that short-term exposure to cold, as well as β3-adrenergic stimulation, causes a significant induction of FGF21 mRNA levels in BAT, without a concomitant increase in FGF21 plasma levels. This finding opens new routes for the potential use of pharmaceuticals that could induce FGF21 and, hence, activate BAT thermogenesis.

Highlights

Fibroblast growth factor (FGF)-21 belongs to the family of atypical FGFs that lack the conventional heparin-binding domain [1,2] and can diffuse away from their tissues of origin to function as hormones
This induction is restricted to Brown adipose tissue (BAT), whereas no change is observed in liver and white adipose tissue (WAT)
BAT is heavily innervated by sympathetic nerves and is responsible for thermogenesis during cold exposure. β3adrenergic receptor agonists cause an increase in energy expenditure that is comparable to that induced by cold in both rodents and humans [19]

Summary

Introduction

Fibroblast growth factor (FGF)-21 belongs to the family of atypical FGFs that lack the conventional heparin-binding domain [1,2] and can diffuse away from their tissues of origin to function as hormones. FGF21 is abundantly expressed in liver, pancreas and white adipose tissue (WAT) [3,4]. It signals through cell-surface complexes of FGF receptors with the transmembrane protein β-Klotho [5,6,7,8]. The limited β-Klotho expression in metabolically competent liver, pancreas and adipose tissue permits FGF21 to selectively target these tissues, allowing this factor to influence glucose, lipid and body weight homeostasis [8,9]. FGF21 is involved in the adaptation of the body to starvation and acts to regulate fatty acid oxidation and ketone formation. The transcription factor peroxisome proliferator–activated receptor (PPAR)α is a critical regulator of FGF21 [10]

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