MiR-221 negatively regulates inflammation and insulin sensitivity in white adipose tissue by repression of sirtuin-1 (SIRT1).

Abstract

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.