Lv Yi-Fan, Yu Jing, Sheng Yun-Lu, Huang Min, Kong Xiao-Cen, Di Wenj-Juan, Liu Juan, Zhou Hong, Liang Hui, Ding Guo-Xian
Department of Gerontology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Department of Endocrinology, Nanjing First Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Endocrinology. 2018 Jan 1;159(1):310-322. doi: 10.1210/en.2017-00566.
Physiological levels of glucocorticoids (GCs) are required for proper metabolic control, and excessive GC action has been linked to a variety of pandemic metabolic diseases. MicroRNA (miRNA)-19b plays a critical role in the pathogenesis of GC-induced metabolic diseases. This study explored the potential of miRNA-based therapeutics targeting adipose tissue. Our results showed that overexpressed miR-19b in stromal vascular fraction (SVF) cells derived from subcutaneous adipose tissue had the same effects as dexamethasone (DEX) treatment on the inhibition of adipose browning and oxygen consumption rate. The inhibition of miR-19b blocked DEX-mediated suppression of the expression of browning marker genes as well as the oxygen consumption rate in differentiated SVF cells derived from subcutaneous and brown adipose tissue. Overexpressed miR-19b in SVF cells derived from brown adipose tissue had the same effects as DEX treatment on the inhibition of brown adipose differentiation and energy expenditure. Glucocorticoids transcriptionally regulate the expression of miR-19b via a GC receptor-mediated direct DNA binding mechanism. This study confirmed that miR-19b is an essential target for GC-mediated control of adipose tissue browning. It is hoped that the plasticity of the adipose organ can be exploited in the next generation of therapeutic strategies to combat the increasing incidence of metabolic diseases, including obesity and diabetes.
糖皮质激素（GCs）的生理水平对于适当的代谢控制是必需的，而过量的GC作用与多种流行的代谢性疾病有关。微小RNA（miRNA）-19b在GC诱导的代谢性疾病发病机制中起关键作用。本研究探讨了基于miRNA的靶向脂肪组织治疗方法的潜力。我们的结果表明，在源自皮下脂肪组织的基质血管成分（SVF）细胞中过表达的miR-19b对脂肪褐变和氧消耗率的抑制作用与地塞米松（DEX）处理相同。抑制miR-19b可阻断DEX介导的对源自皮下和棕色脂肪组织的分化SVF细胞中褐变标记基因表达以及氧消耗率的抑制。在源自棕色脂肪组织的SVF细胞中过表达的miR-19b对棕色脂肪分化和能量消耗的抑制作用与DEX处理相同。糖皮质激素通过GC受体介导的直接DNA结合机制转录调控miR-19b的表达。本研究证实miR-19b是GC介导的脂肪组织褐变控制的重要靶点。希望在下一代治疗策略中能够利用脂肪器官的可塑性来应对包括肥胖症和糖尿病在内的代谢性疾病发病率不断上升的问题。
