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

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 w...

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Vydáno v:	Cell metabolism Ročník 24; číslo 1; s. 130
Hlavní autoři:	Ramage, Lynne E, Akyol, Murat, Fletcher, Alison M, Forsythe, John, Nixon, Mark, Carter, Roderick N, van Beek, Edwin J R, Morton, Nicholas M, Walker, Brian R, Stimson, Roland H
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 12.07.2016
Témata:	Adipocytes - drug effects Adipocytes - metabolism Adipose Tissue, Brown - diagnostic imaging Adipose Tissue, Brown - drug effects Adipose Tissue, Brown - metabolism Animals Anthropometry Biopsy Cells, Cultured Cold Temperature Energy Metabolism - drug effects Fluorodeoxyglucose F18 - metabolism Gene Expression Regulation - drug effects Glucocorticoids - pharmacology Humans Male Mice RNA, Messenger - genetics RNA, Messenger - metabolism Skin Temperature - drug effects Species Specificity Uncoupling Protein 1 - genetics Uncoupling Protein 1 - metabolism Young Adult
ISSN:	1932-7420, 1932-7420
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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.
AbstractList	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. 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.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.
Author	Forsythe, John Nixon, Mark Morton, Nicholas M Stimson, Roland H Akyol, Murat Carter, Roderick N Walker, Brian R Ramage, Lynne E Fletcher, Alison M van Beek, Edwin J R
Author_xml	– sequence: 1 givenname: Lynne E surname: Ramage fullname: Ramage, Lynne E organization: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK – sequence: 2 givenname: Murat surname: Akyol fullname: Akyol, Murat organization: Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, Scotland, UK – sequence: 3 givenname: Alison M surname: Fletcher fullname: Fletcher, Alison M organization: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK – sequence: 4 givenname: John surname: Forsythe fullname: Forsythe, John organization: Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, Scotland, UK – sequence: 5 givenname: Mark surname: Nixon fullname: Nixon, Mark organization: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK – sequence: 6 givenname: Roderick N surname: Carter fullname: Carter, Roderick N organization: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK – sequence: 7 givenname: Edwin J R surname: van Beek fullname: van Beek, Edwin J R organization: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK – sequence: 8 givenname: Nicholas M surname: Morton fullname: Morton, Nicholas M organization: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK – sequence: 9 givenname: Brian R surname: Walker fullname: Walker, Brian R organization: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK – sequence: 10 givenname: Roland H surname: Stimson fullname: Stimson, Roland H email: roland.stimson@ed.ac.uk organization: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK. Electronic address: roland.stimson@ed.ac.uk
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SubjectTerms	Adipocytes - drug effects Adipocytes - metabolism Adipose Tissue, Brown - diagnostic imaging Adipose Tissue, Brown - drug effects Adipose Tissue, Brown - metabolism Animals Anthropometry Biopsy Cells, Cultured Cold Temperature Energy Metabolism - drug effects Fluorodeoxyglucose F18 - metabolism Gene Expression Regulation - drug effects Glucocorticoids - pharmacology Humans Male Mice RNA, Messenger - genetics RNA, Messenger - metabolism Skin Temperature - drug effects Species Specificity Uncoupling Protein 1 - genetics Uncoupling Protein 1 - metabolism Young Adult
Title	Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation
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