Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

Francesca Maria Raffaelli; Julia Resch; Rebecca Oelkrug; K. Alexander Iwen; Jens Mittag

doi:10.1038/s41598-020-77143-6

Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

Francesca Maria Raffaelli, Julia Resch, Rebecca Oelkrug, K. Alexander Iwen, Jens Mittag^*

^*Corresponding author for this work

Institute of Endocrinology and Diabetes

Abstract

Brown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.

Original language	English
Article number	20203
Journal	Scientific Reports
Volume	10
Issue number	1
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-020-77143-6
Publication status	Published - 12.2020

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

DFG Research Classification Scheme

2.22-17 Endocrinology, Diabetology, Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41598-020-77143-6

Cite this

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title = "Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice",

abstract = "Brown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.",

author = "Raffaelli, {Francesca Maria} and Julia Resch and Rebecca Oelkrug and Iwen, {K. Alexander} and Jens Mittag",

note = "Funding Information: We thank the animal facility (GTH) at the University of L{\"u}beck for excellent caretaking. This study was supported by the German Research Foundation (DFG) in the framework of the GRK1957 “Adipocyte-Brain-Crosstalk” and the Heisenberg Program Mi1242/2-2. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

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AU - Iwen, K. Alexander

AU - Mittag, Jens

N1 - Funding Information: We thank the animal facility (GTH) at the University of Lübeck for excellent caretaking. This study was supported by the German Research Foundation (DFG) in the framework of the GRK1957 “Adipocyte-Brain-Crosstalk” and the Heisenberg Program Mi1242/2-2. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

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N2 - Brown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.

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Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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CRC/Transregio TRR 296 LocoTact: Local control of TH action

Cite this

Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

CRC/Transregio TRR 296 LocoTact: Local control of TH action

Cite this