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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Popis
Shrnutí: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.
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ISSN:1932-7420
1932-7420
DOI:10.1016/j.cmet.2016.06.011