title: Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation.
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.
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Ramage
authors.affiliation: Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, Scotland, UK.
authors.forename: Murat
authors.initials: M
authors.lastname: Akyol
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Fletcher
authors.affiliation: Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, Scotland, UK.
authors.forename: John
authors.initials: J
authors.lastname: Forsythe
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Nixon
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Roderick N
authors.initials: RN
authors.lastname: Carter
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Edwin J R
authors.initials: EJ
authors.lastname: van Beek
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Morton
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK. Electronic address: roland.stimson@ed.ac.uk.
authors.forename: Roland H
authors.initials: RH
authors.lastname: Stimson
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000886:Anthropometry; D001706:Biopsy; D002478:Cells, Cultured; D003080:Cold Temperature; D004734:Energy Metabolism / Q000187:drug effects; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012881:Skin Temperature / Q000187:drug effects; D013045:Species Specificity; D000071256:Uncoupling Protein 1 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D000071256:Uncoupling Protein 1; D019788:Fluorodeoxyglucose F18