Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue.
Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue.
复制标题
糖皮质激素转录调节 miR-27b 表达通过抑制白色脂肪组织褐变促进体内脂肪积累
作者：
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
长期糖皮质激素（GC）治疗可引起中枢脂肪积累和代谢功能障碍。我们证明了microRNA-27b （miR-27b）在gc诱导的中枢脂肪堆积的发病机制中起着核心作用。过表达miR-27b与地塞米松（DEX）治疗在抑制棕色脂肪分化和原代脂肪细胞能量消耗方面具有相同的效果。相反，拮抗miR-27b功能可阻止DEX抑制棕色脂肪组织特异性基因的表达。GC通过GC受体介导的直接dna结合机制转录调节miR-27b的表达，miR-27b通过靶向Prdm16的3′未翻译区抑制白色脂肪组织（WAT）的褐变。在体内，在dex处理的小鼠中，拮抗miR-27b功能导致WAT内棕色脂肪细胞的有效诱导，并改善gc诱导的中枢脂肪积累。总之，这些结果表明miR-27b作为GC的中心靶点和Prdm16的上游调节剂来控制WAT的褐变，因此可能是预防肥胖的潜在靶点。
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.