title: Essential roles of 11β-HSD1 in regulating brown adipocyte function.
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.
authors.affiliation: Department of Gerontology, First Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaocen
authors.initials: X
authors.lastname: Kong
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.forename: Hanmei
authors.initials: H
authors.lastname: Qi
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Di
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Juanmin
authors.initials: J
authors.lastname: Zha
authors.forename: Shan
authors.initials: S
authors.lastname: Lv
authors.forename: Aisen
authors.initials: A
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.forename: Miao
authors.initials: M
authors.lastname: Hu
authors.forename: Yujie
authors.initials: Y
authors.lastname: Li
authors.forename: Jianhua
authors.initials: J
authors.lastname: Bi
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Hu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Guoxian
authors.initials: G
authors.lastname: Ding
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology* / Q000201:enzymology; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000201:enzymology; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D017931:DNA Primers; D055785:Gene Knockdown Techniques; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D017931:DNA Primers; D010879:Piperazines; D013449:Sulfonamides; D013844:Thiazoles; C474501:3-chloro-2-methyl-N-(4-(2-(4-methyl-1-piperazinyl)-2-oxoethyl)-1,3-thiazol-2-yl)benzenesulfonamide; D000096926:Benzenesulfonamides