Glucocorticoid-Induced Obesity Develops Independently of UCP1

Summary: An excess of glucocorticoids leads to the development of obesity in both mice and humans, but the mechanism for this is unknown. Here, we determine the extent to which decreased BAT thermogenic capacity (as a result of glucocorticoid treatment) contributes to the development of obesity. Con...

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Main Authors: Ineke H.N. Luijten, Katie Brooks, Nathalie Boulet, Irina G. Shabalina, Ankita Jaiprakash, Bo Carlsson, Alexander W. Fischer, Barbara Cannon, Jan Nedergaard
Format: Article
Language:English
Published: Elsevier 2019-05-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719305066
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author Ineke H.N. Luijten
Katie Brooks
Nathalie Boulet
Irina G. Shabalina
Ankita Jaiprakash
Bo Carlsson
Alexander W. Fischer
Barbara Cannon
Jan Nedergaard
author_facet Ineke H.N. Luijten
Katie Brooks
Nathalie Boulet
Irina G. Shabalina
Ankita Jaiprakash
Bo Carlsson
Alexander W. Fischer
Barbara Cannon
Jan Nedergaard
author_sort Ineke H.N. Luijten
collection DOAJ
description Summary: An excess of glucocorticoids leads to the development of obesity in both mice and humans, but the mechanism for this is unknown. Here, we determine the extent to which decreased BAT thermogenic capacity (as a result of glucocorticoid treatment) contributes to the development of obesity. Contrary to previous suggestions, we show that only in mice housed at thermoneutrality (30°C) does corticosterone treatment reduce total BAT UCP1 protein. This reduction is reflected in reduced brown adipocyte cellular and mitochondrial UCP1-dependent respiration. However, glucocorticoid-induced obesity develops to the same extent in animals housed at 21°C and 30°C, whereas total BAT UCP1 protein levels differ 100-fold between the two groups. In corticosterone-treated wild-type and UCP1 knockout mice housed at 30°C, obesity also develops to the same extent. Thus, our results demonstrate that the development of glucocorticoid-induced obesity is not caused by a decreased UCP1-dependent thermogenic capacity. : Glucocorticoid treatment induces obesity, and reduced brown fat thermogenesis has been suggested to be the cause. However, Luijten et al. show here that this is not the case, nor is it fully explainable by overeating. Thus, glucocorticoids channel food energy into lipid storage through a currently unexplained pathway. Keywords: uncoupling protein 1, corticosterone, obesity, thermogenesis, energy balance, brown adipose tissue, thermoneutrality, cold exposure
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spelling doaj.art-3afa71a84a774e268ddc95c8709394e62022-12-21T23:39:56ZengElsevierCell Reports2211-12472019-05-0127616861698.e5Glucocorticoid-Induced Obesity Develops Independently of UCP1Ineke H.N. Luijten0Katie Brooks1Nathalie Boulet2Irina G. Shabalina3Ankita Jaiprakash4Bo Carlsson5Alexander W. Fischer6Barbara Cannon7Jan Nedergaard8Department of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenDepartment of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenDepartment of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenDepartment of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenDepartment of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenDepartment of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenDepartment of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg Eppendorf, Hamburg, GermanyDepartment of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, SwedenDepartment of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden; Corresponding authorSummary: An excess of glucocorticoids leads to the development of obesity in both mice and humans, but the mechanism for this is unknown. Here, we determine the extent to which decreased BAT thermogenic capacity (as a result of glucocorticoid treatment) contributes to the development of obesity. Contrary to previous suggestions, we show that only in mice housed at thermoneutrality (30°C) does corticosterone treatment reduce total BAT UCP1 protein. This reduction is reflected in reduced brown adipocyte cellular and mitochondrial UCP1-dependent respiration. However, glucocorticoid-induced obesity develops to the same extent in animals housed at 21°C and 30°C, whereas total BAT UCP1 protein levels differ 100-fold between the two groups. In corticosterone-treated wild-type and UCP1 knockout mice housed at 30°C, obesity also develops to the same extent. Thus, our results demonstrate that the development of glucocorticoid-induced obesity is not caused by a decreased UCP1-dependent thermogenic capacity. : Glucocorticoid treatment induces obesity, and reduced brown fat thermogenesis has been suggested to be the cause. However, Luijten et al. show here that this is not the case, nor is it fully explainable by overeating. Thus, glucocorticoids channel food energy into lipid storage through a currently unexplained pathway. Keywords: uncoupling protein 1, corticosterone, obesity, thermogenesis, energy balance, brown adipose tissue, thermoneutrality, cold exposurehttp://www.sciencedirect.com/science/article/pii/S2211124719305066
spellingShingle Ineke H.N. Luijten
Katie Brooks
Nathalie Boulet
Irina G. Shabalina
Ankita Jaiprakash
Bo Carlsson
Alexander W. Fischer
Barbara Cannon
Jan Nedergaard
Glucocorticoid-Induced Obesity Develops Independently of UCP1
Cell Reports
title Glucocorticoid-Induced Obesity Develops Independently of UCP1
title_full Glucocorticoid-Induced Obesity Develops Independently of UCP1
title_fullStr Glucocorticoid-Induced Obesity Develops Independently of UCP1
title_full_unstemmed Glucocorticoid-Induced Obesity Develops Independently of UCP1
title_short Glucocorticoid-Induced Obesity Develops Independently of UCP1
title_sort glucocorticoid induced obesity develops independently of ucp1
url http://www.sciencedirect.com/science/article/pii/S2211124719305066
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AT ankitajaiprakash glucocorticoidinducedobesitydevelopsindependentlyofucp1
AT bocarlsson glucocorticoidinducedobesitydevelopsindependentlyofucp1
AT alexanderwfischer glucocorticoidinducedobesitydevelopsindependentlyofucp1
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