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生理糖皮质激素节律是棕色脂肪组织功能的重要调节剂。

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

机构信息

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.

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.

出版信息

Mol Metab. 2021 May;47:101179. doi: 10.1016/j.molmet.2021.101179. Epub 2021 Feb 3.

DOI:10.1016/j.molmet.2021.101179
PMID:33548499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7907824/
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.

摘要

目的

棕色脂肪组织 (BAT) 的代谢活性呈现出很强的昼夜节律，但目前尚不清楚这种节律是如何调节的。由于循环中的皮质酮水平与 BAT 摄取甘油三酯衍生脂肪酸 (FA) 的节律相吻合，我们研究了皮质酮是否调节 BAT 的昼夜节律。

方法

通过在小鼠皮下植入皮质酮释放微球来使皮质酮水平平稳化，从而导致循环中的皮质酮水平保持稳定。

结果

皮质酮节律的平稳化导致 BAT 摄取甘油三酯衍生脂肪酸的昼夜节律完全丧失。这种作用独立于 (棕色) 脂肪细胞中糖皮质激素受体的表达，也不是由于时钟基因表达失调或过度暴露于糖皮质激素引起的，而是似乎通过 BAT 交感神经支配的减少来介导。在高脂血症和代谢综合征的小鼠模型中，长期实验性地使皮质酮平稳化——从而使 BAT 功能的节律化——导致肥胖。

结论

这项研究强调了生理节律的糖皮质激素是调节 BAT 功能的重要因素，对于维持代谢健康是必不可少的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/01a701964c6b/figs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/979b415e31ae/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/d8b0dec3b798/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/3ecf78c27eb8/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/9e6ec767dfdf/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/9b804d358a1d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/b42af7808f72/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/cad084352bfd/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/b1e0e6142e76/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/1fcabce920d0/figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/baa5740a5343/figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/01a701964c6b/figs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/979b415e31ae/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/d8b0dec3b798/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/3ecf78c27eb8/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/9e6ec767dfdf/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/9b804d358a1d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/b42af7808f72/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/cad084352bfd/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/b1e0e6142e76/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/1fcabce920d0/figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/baa5740a5343/figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda3/7907824/01a701964c6b/figs5.jpg

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