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

    1. Guoxian Ding1
    1. 1Department of Gerontology, First Hospital Affiliated to Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People's Republic of China
      2Departments of Pathophysiology, Nanjing Medical University, Nanjing, People's Republic of China
      3Preventive Medicine, Feinberg School of Medicine Northwestern University, Chicago, Illinois, USA
      4Department of Pharmaceutical Chemistry, China Pharmaceutical University, Nanjing, People's Republic of China
      5Metabolic Syndrome Research Center of Central South University, Institute of Metabolism and Endocrinology, the Second Xiangya Hospital of Central South University, Changsha, People's Republic of China
    1. (Correspondence should be addressed to G Ding; Email: dinggx{at}njmu.edu.cn)

    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.

    Keywords
    • Revision received 22 November 2012
    • Accepted 29 November 2012
    • Made available online as an Accepted Preprint 29 November 2012
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