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A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function. 2021
Jan Kroon, and
Maaike Schilperoort, and
Wietse In Het Panhuis, and
Rosa van den Berg, and
Lotte van Doeselaar, and
Cristy R C Verzijl, and
Nikki van Trigt, and
Isabel M Mol, and
Hetty H C M Sips, and
Jose K van den Heuvel, and
Lisa L Koorneef, and
Ronald J van der Sluis, and
Anna Fenzl, and
Florian W Kiefer, and
Sabine Vettorazzi, and
Jan P Tuckermann, and
Nienke R Biermasz, and
Onno C Meijer, and
Patrick C N Rensen, and
Sander Kooijman
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.
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. Corticosterone levels were flattened by implanting mice with subcutaneous corticosterone-releasing pellets, resulting in constant circulating corticosterone levels. 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. This study highlights that a physiological rhythm in glucocorticoids is an important regulator of BAT function and essential for the maintenance of metabolic health.
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