A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function
Objective: Brown adipose tissue (BAT) displays a strong circadian rhythm in metabolic activity, but it is unclear how this rhythm is regulated. As circulating levels of corticosterone coincide with the rhythm of triglyceride-derived fatty acid (FA) uptake by BAT, we investigated whether corticostero...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-05-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877821000193 |
| _version_ | 1818933783713284096 |
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| author | Jan Kroon Maaike Schilperoort Wietse In het Panhuis Rosa van den Berg Lotte van Doeselaar Cristy R.C. Verzijl Nikki van Trigt Isabel M. Mol Hetty H.C.M. Sips Jose K. van den Heuvel Lisa L. Koorneef Ronald J. van der Sluis Anna Fenzl Florian W. Kiefer Sabine Vettorazzi Jan P. Tuckermann Nienke R. Biermasz Onno C. Meijer Patrick C.N. Rensen Sander Kooijman |
| author_facet | Jan Kroon Maaike Schilperoort Wietse In het Panhuis Rosa van den Berg Lotte van Doeselaar Cristy R.C. Verzijl Nikki van Trigt Isabel M. Mol Hetty H.C.M. Sips Jose K. van den Heuvel Lisa L. Koorneef Ronald J. van der Sluis Anna Fenzl Florian W. Kiefer Sabine Vettorazzi Jan P. Tuckermann Nienke R. Biermasz Onno C. Meijer Patrick C.N. Rensen Sander Kooijman |
| author_sort | Jan Kroon |
| collection | DOAJ |
| description | Objective: Brown adipose tissue (BAT) displays a strong circadian rhythm in metabolic activity, but it is unclear how this rhythm is regulated. As circulating levels of corticosterone coincide with the rhythm of triglyceride-derived fatty acid (FA) uptake by BAT, we investigated whether corticosterone regulates BAT circadian rhythm. Methods: Corticosterone levels were flattened by implanting mice with subcutaneous corticosterone-releasing pellets, resulting in constant circulating corticosterone levels. Results: Flattened corticosterone rhythm caused a complete loss of circadian rhythm in triglyceride-derived fatty acid uptake by BAT. This effect was independent of glucocorticoid receptor expression in (brown) adipocytes and was not caused by deregulation of clock gene expression or overexposure to glucocorticoids, but rather seemed mediated by reduced sympathetic innervation of BAT. In a mouse model of hyperlipidemia and metabolic syndrome, long-term experimental flattening of corticosterone − and thus rhythm in BAT function − resulted in adiposity. Conclusions: This study highlights that a physiological rhythm in glucocorticoids is an important regulator of BAT function and essential for the maintenance of metabolic health. |
| first_indexed | 2024-12-20T04:53:52Z |
| format | Article |
| id | doaj.art-1ca61bd60fff4069a39d7542195ccab5 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-20T04:53:52Z |
| publishDate | 2021-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-1ca61bd60fff4069a39d7542195ccab52022-12-21T19:52:46ZengElsevierMolecular Metabolism2212-87782021-05-0147101179A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue functionJan Kroon0Maaike Schilperoort1Wietse In het Panhuis2Rosa van den Berg3Lotte van Doeselaar4Cristy R.C. Verzijl5Nikki van Trigt6Isabel M. Mol7Hetty H.C.M. Sips8Jose K. van den Heuvel9Lisa L. Koorneef10Ronald J. van der Sluis11Anna Fenzl12Florian W. Kiefer13Sabine Vettorazzi14Jan P. Tuckermann15Nienke R. Biermasz16Onno C. Meijer17Patrick C.N. Rensen18Sander Kooijman19Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; Department of Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, the NetherlandsClinical Division of Endocrinology and Metabolism, Department of Medicine, Medical University of Vienna, Vienna, AustriaClinical Division of Endocrinology and Metabolism, Department of Medicine, Medical University of Vienna, Vienna, AustriaInstitute for Comparative Molecular Endocrinology, University of Ulm, Ulm, GermanyInstitute for Comparative Molecular Endocrinology, University of Ulm, Ulm, GermanyDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; Department of Endocrinology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, ChinaDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; Corresponding author. Department of Medicine, Division of Endocrinology Leiden University Medical Center Albinusdreef 2, 2333ZA, Leiden, the Netherlands.Objective: Brown adipose tissue (BAT) displays a strong circadian rhythm in metabolic activity, but it is unclear how this rhythm is regulated. As circulating levels of corticosterone coincide with the rhythm of triglyceride-derived fatty acid (FA) uptake by BAT, we investigated whether corticosterone regulates BAT circadian rhythm. Methods: Corticosterone levels were flattened by implanting mice with subcutaneous corticosterone-releasing pellets, resulting in constant circulating corticosterone levels. Results: Flattened corticosterone rhythm caused a complete loss of circadian rhythm in triglyceride-derived fatty acid uptake by BAT. This effect was independent of glucocorticoid receptor expression in (brown) adipocytes and was not caused by deregulation of clock gene expression or overexposure to glucocorticoids, but rather seemed mediated by reduced sympathetic innervation of BAT. In a mouse model of hyperlipidemia and metabolic syndrome, long-term experimental flattening of corticosterone − and thus rhythm in BAT function − resulted in adiposity. Conclusions: This study highlights that a physiological rhythm in glucocorticoids is an important regulator of BAT function and essential for the maintenance of metabolic health.http://www.sciencedirect.com/science/article/pii/S2212877821000193Brown adipose tissueCircadian RhythmCorticosteroneGlucocorticoid receptor |
| spellingShingle | Jan Kroon Maaike Schilperoort Wietse In het Panhuis Rosa van den Berg Lotte van Doeselaar Cristy R.C. Verzijl Nikki van Trigt Isabel M. Mol Hetty H.C.M. Sips Jose K. van den Heuvel Lisa L. Koorneef Ronald J. van der Sluis Anna Fenzl Florian W. Kiefer Sabine Vettorazzi Jan P. Tuckermann Nienke R. Biermasz Onno C. Meijer Patrick C.N. Rensen Sander Kooijman A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function Molecular Metabolism Brown adipose tissue Circadian Rhythm Corticosterone Glucocorticoid receptor |
| title | A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function |
| title_full | A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function |
| title_fullStr | A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function |
| title_full_unstemmed | A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function |
| title_short | A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function |
| title_sort | physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function |
| topic | Brown adipose tissue Circadian Rhythm Corticosterone Glucocorticoid receptor |
| url | http://www.sciencedirect.com/science/article/pii/S2212877821000193 |
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