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

Cell Metab. 2016 Jul 12;24(1):130-41. doi: 10.1016/j.cmet.2016.06.011.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Glucocorticoids
  • RNA, Messenger
  • Uncoupling Protein 1
  • Fluorodeoxyglucose F18