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
Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
Department of General Surgery, The First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
Diabetes. 2015 Feb;64(2):393-404. doi: 10.2337/db14-0395. Epub 2014 Sep 3.
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.
长期糖皮质激素（GC）治疗会导致中心性脂肪堆积和代谢功能障碍。我们证明，微小RNA-27b（miR-27b）在GC诱导的中心性脂肪堆积的发病机制中起核心作用。miR-27b的过表达对棕色脂肪分化的抑制作用以及对原代脂肪细胞能量消耗的影响与地塞米松（DEX）治疗相同。相反，拮抗miR-27b的功能可防止DEX对棕色脂肪组织特异性基因表达的抑制。GCs通过GC受体介导的直接DNA结合机制转录调控miR-27b的表达，并且miR-27b通过靶向Prdm16的3'非翻译区来抑制白色脂肪组织（WAT）的褐变。在体内，在DEX处理的小鼠中拮抗miR-27b的功能可有效诱导WAT内的棕色脂肪细胞，并改善GC诱导的中心性脂肪堆积。总体而言，这些结果表明，miR-27b作为GC的核心靶点以及Prdm16的上游调节因子，可控制WAT的褐变，因此可能是预防肥胖症的潜在靶点。
