Abstract:
The most common form of hypercortisolism is iatrogenic Cushing\'s syndrome. Lipodystrophy and metabolic disorders can result from the use of exogenous glucocorticoids (GC). Adipocytes play an important role in the production of circulating exosomal microRNAs, and knockdown of Dicer promotes lipodystrophy. The aim of this study is to investigate the effect of GCs on epididymal fat and to assess their influence on circulating microRNAs associated with fat turnover. The data indicate that despite the reduction in adipocyte volume due to increased lipolysis and apoptosis, there is no difference in tissue mass, suggesting that epididymal fat pad, related to animal size, is not affected by GC treatment. Although high concentrations of GC have no direct effect on epididymal microRNA-150-5p expression, GC can induce epididymal adipocyte uptake of microRNA-150-5p, which regulates transcription factor Ppar gamma during adipocyte maturation. In addition, GC treatment increased lipolysis and decreased glucose-derived lipid and glycerol incorporation. In conclusion, the similar control and GC epididymal fat mass results from increased dense fibrogenic tissue and decreased adipocyte volume induced by the lipolytic effect of GC. These findings demonstrate the complexity of epididymal fat. They also highlight how this disease alters fat distribution. This study is the first in a series published by our laboratory showing the detailed mechanism of adipocyte turnover in this disease.
摘要:
皮质醇增多症最常见的形式是医源性库欣综合征。使用外源性糖皮质激素(GC)可导致脂肪营养不良和代谢紊乱。脂肪细胞在循环外泌体microRNAs的产生中发挥重要作用,和敲除Dicer促进脂肪营养不良。这项研究的目的是研究GCs对附睾脂肪的影响,并评估它们对与脂肪周转相关的循环microRNAs的影响。数据表明,尽管由于脂解和细胞凋亡增加而导致脂肪细胞体积减少,组织质量没有差异,表明附睾脂肪垫,与动物的大小有关,不受GC处理的影响。尽管高浓度的GC对附睾microRNA-150-5p表达没有直接影响,GC可以诱导附睾脂肪细胞摄取microRNA-150-5p,在脂肪细胞成熟过程中调节转录因子PPARγ。此外,GC处理增加了脂解并减少了葡萄糖衍生的脂质和甘油的掺入。总之,相似的对照和GC附睾脂肪量是由于GC的脂肪分解作用引起的致密纤维化组织增加和脂肪细胞体积减少。这些发现证明了附睾脂肪的复杂性。他们还强调了这种疾病如何改变脂肪分布。这项研究是我们实验室发表的一系列研究中的第一项,该研究显示了这种疾病中脂肪细胞周转的详细机制。