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

Xiaocen Kong, Jing Yu, Jianhua Bi, Hanmei Qi, Wenjuan Di, Lin Wu, Long Wang, Juanmin Zha, Shan Lv, Feng Zhang, Yan Li, Fang Hu, Feng Liu, Hong Zhou, Juan Liu, Guoxian Ding

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56 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)393-404
Number of pages12
JournalDiabetes
Volume64
Issue number2
DOIs
StatePublished - Feb 1 2015

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Kong, X., Yu, J., Bi, J., Qi, H., Di, W., Wu, L., Wang, L., Zha, J., Lv, S., Zhang, F., Li, Y., Hu, F., Liu, F., Zhou, H., Liu, J., & Ding, G. (2015). Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue. Diabetes, 64(2), 393-404. https://doi.org/10.2337/db14-0395