miR-221 negatively regulates inflammation and insulin sensitivity in white adipose tissue by repression of sirtuin-1 (SIRT1)
miR-221 negatively regulates inflammation and insulin sensitivity in white adipose tissue by repression of sirtuin-1 (SIRT1)
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DOI：
10.1002/jcb.26589
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发表时间：
2018-08-01
影响因子：
4
通讯作者：
Peng, Jian
中科院分区：
文献类型：
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作者：
Peng, Jie;Zhou, Yuanfei;Peng, Jian
众所周知，肥胖引起的白色脂肪组织炎症是胰岛素抵抗和2型糖尿病的重要原因。SIRT 1是白色脂肪组织炎症反应途径的重要调节因子。在此，我们发现miR-221在炎症和HFD诱导的肥胖过程中负调控白色脂肪组织中的SIRT 1。miR-221是一种推定的癌基因，已发现其在许多人类肿瘤中过表达。最近，还发现miR-221在肥胖脂肪组织中增加，并且可能参与炎症和胰岛素抵抗。然而，具体机制仍有待阐明。在我们目前的研究中，我们发现miR-221的过表达降低了SIRT 1的蛋白丰度，并在分化的3 T3-L1细胞中引起炎症和胰岛素抵抗。相反，miR-221抑制增加了蛋白水平，改善了炎症，并改善了胰岛素敏感性。此外，EX 527对SIRT 1的抑制显著降低了miR-221抑制剂诱导的炎症和胰岛素抵抗水平的下调。总之，我们的数据表明，miR-221促进白色脂肪组织炎症，并降低肥胖症的胰岛素敏感性，至少部分是通过抑制SIRT 1。
It is well known that obesity-induced white adipose tissue inflammation is an important reason for insulin-resistance and type 2 diabetes mellitus. Sirtuin-1 (SIRT1) is an important regulator of inflammtion response pathways in white adipose tissue. Here, we found that miR-221 negatively regulated SIRT1 in white adipose tissue during inflammation and HFD-induced obesity. MiR-221 is a putative oncogene which has been found overexpressed in a number of human tumors. Recently, it has also found that miR-221 was increased in obese adipose tissue and may be involved in inflammation and insulin-resistance. However the specific mechanism remains to be elucidated. In our present study, we found that overexpression of miR-221 decreased the protein abundance of SIRT1 and caused inflammation and insulin-resistance in differentiated 3T3-L1 cells. Conversely, miR-221 inhibition increased the protein levels, ameliorated inflammation, and improved insulin sensitivity. Moreover, inhibition of SIRT1 by EX527 significantly diminished the downregulation of the inflammation and insulin-resistance levels induced by the miR-221 inhibitor. In conclusion, our data suggest that miR-221 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity, at least in part, through suppressing SIRT1.