Oncotarget

Research Papers:

MiR-377 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity via suppression of sirtuin-1 (SIRT1)

Jie Peng, Yinghui Wu, Zhao Deng, Yuanfei Zhou, Tongxing Song, Yang Yang, Xiaming Zhang, Tao Xu, Mao Xia, Anle Cai, Zuhong Liu and Jian Peng _

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Oncotarget. 2017; 8:70550-70563. https://doi.org/10.18632/oncotarget.19742

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Abstract

Jie Peng1, Yinghui Wu1, Zhao Deng1, Yuanfei Zhou1, Tongxing Song1, Yang Yang1, Xiaming Zhang1, Tao Xu1, Mao Xia1, Anle Cai1, Zuhong Liu1 and Jian Peng1,2

1Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, P. R. China

2The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, P. R. China

Correspondence to:

Jian Peng, email: [email protected]

Keywords: miR-377, SIRT1, obesity, inflammation, insulin-resistance

Received: January 24, 2017     Accepted: June 02, 2017     Published: July 31, 2017

ABSTRACT

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.


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