Essential roles of 11β-HSD1 in regulating brown adipocyte function

J Mol Endocrinol. 2013 Jan 11;50(1):103-13. doi: 10.1530/JME-12-0099. Print 2013 Feb.

Abstract

Brown adipose tissue (BAT) increases energy expenditure and is an attractive therapeutic target for obesity. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), an amplifier of local glucocorticoid activity, has been shown to modulate white adipose tissue (WAT) metabolism and function. In this study, we investigated the roles of 11β-HSD1 in regulating BAT function. We observed a significant increase in the expression of BAT-specific genes, including UCP1, Cidea, Cox7a1, and Cox8b, in BVT.2733 (a selective inhibitor of 11β-HSD1)-treated and 11β-HSD1-deficient primary brown adipocytes of mice. By contrast, a remarkable decrease in BAT-specific gene expression was detected in brown adipocytes when 11β-HSD1 was overexpressed, which effect was reversed by BVT.2733 treatment. Consistent with the in vitro results, expression of a range of genes related to brown fat function in high-fat diet-fed mice treated with BVT.2733. Our results indicate that 11β-HSD1 acts as a vital regulator that controls the expression of genes related to brown fat function and as such may become a potential target in preventing obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism*
  • Adipocytes / cytology*
  • Adipocytes / enzymology
  • Adipose Tissue, Brown / cytology*
  • Adipose Tissue, Brown / enzymology
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cells, Cultured
  • DNA Primers
  • Gene Knockdown Techniques
  • Mice
  • Piperazines / pharmacology
  • Real-Time Polymerase Chain Reaction
  • Sulfonamides / pharmacology
  • Thiazoles / pharmacology

Substances

  • 3-chloro-2-methyl-N-(4-(2-(4-methyl-1-piperazinyl)-2-oxoethyl)-1,3-thiazol-2-yl)benzenesulfonamide
  • DNA Primers
  • Piperazines
  • Sulfonamides
  • Thiazoles
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1