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

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 duri...

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Autores principales: Peng, Jie, Wu, Yinghui, Deng, Zhao, Zhou, Yuanfei, Song, Tongxing, Yang, Yang, Zhang, Xiaming, Xu, Tao, Xia, Mao, Cai, Anle, Liu, Zuhong, Peng, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642576/
https://www.ncbi.nlm.nih.gov/pubmed/29050301
http://dx.doi.org/10.18632/oncotarget.19742
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author Peng, Jie
Wu, Yinghui
Deng, Zhao
Zhou, Yuanfei
Song, Tongxing
Yang, Yang
Zhang, Xiaming
Xu, Tao
Xia, Mao
Cai, Anle
Liu, Zuhong
Peng, Jian
author_facet Peng, Jie
Wu, Yinghui
Deng, Zhao
Zhou, Yuanfei
Song, Tongxing
Yang, Yang
Zhang, Xiaming
Xu, Tao
Xia, Mao
Cai, Anle
Liu, Zuhong
Peng, Jian
author_sort Peng, Jie
collection PubMed
description 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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spelling pubmed-56425762017-10-18 MiR-377 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity via suppression of sirtuin-1 (SIRT1) Peng, Jie Wu, Yinghui Deng, Zhao Zhou, Yuanfei Song, Tongxing Yang, Yang Zhang, Xiaming Xu, Tao Xia, Mao Cai, Anle Liu, Zuhong Peng, Jian Oncotarget Research Paper 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. Impact Journals LLC 2017-07-31 /pmc/articles/PMC5642576/ /pubmed/29050301 http://dx.doi.org/10.18632/oncotarget.19742 Text en Copyright: © 2017 Peng et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Peng, Jie
Wu, Yinghui
Deng, Zhao
Zhou, Yuanfei
Song, Tongxing
Yang, Yang
Zhang, Xiaming
Xu, Tao
Xia, Mao
Cai, Anle
Liu, Zuhong
Peng, Jian
MiR-377 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity via suppression of sirtuin-1 (SIRT1)
title MiR-377 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity via suppression of sirtuin-1 (SIRT1)
title_full MiR-377 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity via suppression of sirtuin-1 (SIRT1)
title_fullStr MiR-377 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity via suppression of sirtuin-1 (SIRT1)
title_full_unstemmed MiR-377 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity via suppression of sirtuin-1 (SIRT1)
title_short MiR-377 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity via suppression of sirtuin-1 (SIRT1)
title_sort mir-377 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity via suppression of sirtuin-1 (sirt1)
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642576/
https://www.ncbi.nlm.nih.gov/pubmed/29050301
http://dx.doi.org/10.18632/oncotarget.19742
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