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

被引:34
作者
Liu, Juan [1 ]
Kong, Xiaocen [1 ]
Wang, Long [1 ]
Qi, Hanmei [1 ]
Di, Wenjuan [1 ]
Zhang, Xiao [3 ]
Wu, Lin [1 ]
Chen, Xia [1 ]
Yu, Jing [1 ]
Zha, Juanmin [1 ]
Lv, Shan [1 ]
Zhang, Aisen [1 ]
Cheng, Peng [1 ]
Hu, Miao [1 ]
Li, Yujie [1 ]
Bi, Jianhua [1 ]
Li, Yan [5 ]
Hu, Fang [5 ]
Zhong, Yi [4 ]
Xu, Yong [2 ]
Ding, Guoxian [1 ]
机构
[1] Nanjing Med Univ, Hosp 1, Dept Gerontol, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Dept Pathophysiol, Nanjing 210029, Jiangsu, Peoples R China
[3] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA
[4] China Pharmaceut Univ, Dept Pharmaceut Chem, Nanjing, Jiangsu, Peoples R China
[5] Cent S Univ, Xiangya Hosp 2, Inst Metab & Endocrinol, Metab Syndrome Res Ctr, Changsha, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
11 beta-hydroxysteroid dehydrogenase type 1; BVT.2733; brown adipose tissue; fatty beta-oxidation; obesity; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; VISCERAL ADIPOSE-TISSUE; SELECTIVE-INHIBITION; INSULIN SENSITIVITY; METABOLIC SYNDROME; GENE-EXPRESSION; FAT; DIFFERENTIATION; OBESITY; OVEREXPRESSION;
D O I
10.1530/JME-12-0099
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Brown adipose tissue (BAT) increases energy expenditure and is an attractive therapeutic target for obesity. 11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-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 11 beta-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 11 beta-HSD1)-treated and 11 beta-HSD1-deficient primary brown adipocytes of mice. By contrast, a remarkable decrease in BAT-specific gene expression was detected in brown adipocytes when 11 beta-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 11 beta-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.
引用
收藏
页码:103 / 113
页数:11
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