Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue

• Published in: Diabetes (New York, N.Y.) Vol. 64; no. 2; pp. 393 - 404
• Main Authors: Kong, Xiaocen, Yu, Jing, Bi, Jianhua, Qi, Hanmei, Di, Wenjuan, Wu, Lin, Wang, Long, Zha, Juanmin, Lv, Shan, Zhang, Feng, Li, Yan, Hu, Fang, Liu, Feng, Zhou, Hong, Liu, Juan, Ding, Guoxian
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-02-2015
• Subjects: Adipocytes; Adipose Tissue - metabolism; Adipose Tissue, Brown - physiology; Adipose Tissue, White - physiology; Animals; Animals, Genetically Modified; Binding sites; Bioenergetics; Dexamethasone - pharmacology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene expression; Gene Expression Regulation - physiology; Metabolism; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Pathogenesis; Rodents; Steroids; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db14-0395

Long-term glucocorticoid (GC) treatment induces central fat accumulation and metabolic dysfunction. We demonstrate that microRNA-27b (miR-27b) plays a central role in the pathogenesis of GC-induced central fat accumulation. Overexpression of miR-27b had the same effects as dexamethasone (DEX) treatment on the inhibition of brown adipose differentiation and the energy expenditure of primary adipocytes. Conversely, antagonizing miR-27b function prevented DEX suppression of the expression of brown adipose tissue-specific genes. GCs transcriptionally regulate miR-27b expression through a GC receptor-mediated direct DNA-binding mechanism, and miR-27b suppresses browning of white adipose tissue (WAT) by targeting the three prime untranslated region of Prdm16. In vivo, antagonizing miR-27b function in DEX-treated mice resulted in the efficient induction of brown adipocytes within WAT and improved GC-induced central fat accumulation. Collectively, these results indicate that miR-27b functions as a central target of GC and as an upstream regulator of Prdm16 to control browning of WAT and, consequently, may represent a potential target in preventing obesity.