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Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation

Ramage, LE; Akyol, M; Fletcher, AM; Forsythe, J; Nixon, M; Carter, RN; van Beek, EJR; ... Stimson, RH; + view all (2016) Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation. Cell Metabolism , 24 (1) pp. 130-141. 10.1016/j.cmet.2016.06.011. Green open access

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Abstract

The discovery of brown adipose tissue (BAT) in adult humans presents a new therapeutic target for metabolic disease; however, little is known about the regulation of human BAT. Chronic glucocorticoid excess causes obesity in humans, and glucocorticoids suppress BAT activation in rodents. We tested whether glucocorticoids regulate BAT activity in humans. In vivo, the glucocorticoid prednisolone acutely increased (18)fluorodeoxyglucose uptake by BAT (measured using PET/CT) in lean healthy men during mild cold exposure (16°C-17°C). In addition, prednisolone increased supraclavicular skin temperature (measured using infrared thermography) and energy expenditure during cold, but not warm, exposure in lean subjects. In vitro, glucocorticoids increased isoprenaline-stimulated respiration and UCP-1 in human primary brown adipocytes, but substantially decreased isoprenaline-stimulated respiration and UCP-1 in primary murine brown and beige adipocytes. The highly species-specific regulation of BAT function by glucocorticoids may have important implications for the translation of novel treatments to activate BAT to improve metabolic health.

Type: Article
Title: Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cmet.2016.06.011
Publisher version: https://doi.org/10.1016/j.cmet.2016.06.011
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Adipocytes, Adipose Tissue, Brown, Animals, Anthropometry, Biopsy, Cells, Cultured, Cold Temperature, Energy Metabolism, Fluorodeoxyglucose F18, Gene Expression Regulation, Glucocorticoids, Humans, Male, Mice, RNA, Messenger, Skin Temperature, Species Specificity, Uncoupling Protein 1, Young Adult
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10053189
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