Obesity is associated with a wide range of metabolic disorders including
inflammation and
insulin-resistance. Sirtuin-1 (
SIRT1) is an important regulator of metabolic homeostasis and stress response pathways in white adipose tissue. However, involvement of
microRNAs (
miRNAs) in regulating
SIRT1 during
obesity-induced
inflammation and
insulin-resistance remains unclear. Here, we found that miR-377 was upregulated in adipose tissue and showed a negative correlation with
SIRT1 in chronic high fat diet (HFD)-fed mice. MiR-377 belongs to a large
miRNA cluster and functions as an important
tumor suppressor in several human
malignancies. Recently, it has also gained considerable attention in oxidative stress and
diabetic nephropathy. In our present study, we found that overexpression of miR-377 decreased
SIRT1 protein abundance and caused
inflammation and
insulin-resistance in differentiated 3T3-L1 cells. Conversely, miR-377 inhibition increased
SIRT1 mRNA and
protein levels, ameliorated
inflammation and improved
insulin sensitivity. Furthermore, we demonstrated that miR-377 targets the 3'-UTR of
SIRT1 mRNA directly, and downregulates
SIRT1 protein abundance. Inhibition of
SIRT1 by EX527 significantly eliminated the downregulation of the
inflammation and
insulin-resistance levels induced by the miR-377 inhibitor. Furthermore,
SIRT1 deficiency intensified adipose tissue
inflammation and
insulin-resistance, resulting in hepatic steatosis in chronic-HFD-fed mice. In conclusion, our findings suggest that miR-377 promotes white adipose tissue
inflammation and decreases
insulin sensitivity in
obesity, at least in part, through suppressing
SIRT1.