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

• Published in: Cell metabolism Vol. 24; no. 1; pp. 130 - 141
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.07.2016; Cell Press
• Subjects: 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: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2016.06.011

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 18fluorodeoxyglucose 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. [Display omitted] •Glucocorticoids acutely increase but chronically suppress BAT activity in humans•Glucocorticoids increase UCP-1 and respiration in human brown adipocytes•Glucocorticoids decrease UCP-1 and respiration in murine brown and beige adipocytes•Species-specific differences exist in the regulation of BAT activation The regulation of brown adipose tissue (BAT) in humans is not well understood. Ramage et al. show that glucocorticoids acutely increase BAT in vivo and in vitro in humans through increasing UCP-1. However, glucocorticoids decrease UCP-1 in murine beige/ brown adipocytes, identifying species-specific differences in the regulation of BAT function.