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Mol Metab. 2021 May;47:101179. doi: 10.1016/j.molmet.2021.101179. Epub 2021 Feb 03.

A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function.

Molecular metabolism

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

Affiliations

  1. Department 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.
  2. Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; Department of Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
  3. Clinical Division of Endocrinology and Metabolism, Department of Medicine, Medical University of Vienna, Vienna, Austria.
  4. Institute for Comparative Molecular Endocrinology, University of Ulm, Ulm, Germany.
  5. Department 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, China.
  6. Department 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. Electronic address: [email protected].

PMID: 33548499 PMCID: PMC7907824 DOI: 10.1016/j.molmet.2021.101179

Abstract

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.

Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.

Keywords: Brown adipose tissue; Circadian Rhythm; Corticosterone; Glucocorticoid receptor

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