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miR‐221 negatively regulates inflammation and insulin sensitivity in white adipose tissue by repression of sirtuin‐1 (SIRT1)

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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… Click to show full 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.

Keywords: insulin; mir 221; inflammation; white adipose; adipose tissue

Journal Title: Journal of Cellular Biochemistry
Year Published: 2018

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