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LncRNA TUG1 reduces inflammation and enhances insulin sensitivity in white adipose tissue by regulating miR-204/SIRT1 axis in obesity mice

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Abstract

Prevalence of obesity becomes an important health issue worldwide, but the management of obesity remains unsatisfied. This study aimed to explore the mechanism of long non-coding RNA TUG/miR-204/SIRT1 axis, which was involved in the pathogenesis of obesity. Obesity mouse model was induced by high-fat diet and treated with taurine upregulated gene1 (TUG1) virus via tail intravenous injection. Then, body weight, serum glucose, insulin tolerance, testicular fat weight were detected, as well as the expression of TUG1, microRNA-204 (miR-204), sirtuin1 (SIRT1), and inflammation and fatty accumulation associated proteins and cytokines. Regulatory relationship between TUG1/SIRT1 and miR-204 was confirmed by dual-luciferase reporter activity assay. A high-glucose-induced 3T3-L1 cell model was also constructed to explore the regulatory mechanism of TUG/miR-204/SIRT1 axis in the pathogenesis of obesity at cell level after altering the expression of TUG1, miR-204, and SIRT1. Overexpression of TUG1 could significantly attenuate the weight, serum glucose, glucose, insulin tolerance, fatty accumulation, and inflammation in obesity mice, as well as the elevation of miR-204, but increase the expression of SIRT1, phosphorylated AKT (p-AKT), glucose transporter4 (GLUT4), and peroxisome proliferator activated receptorγ (PPARγ). Both TUG1 and SIRT1 were targets of miR-204 and could be negatively regulated by miR-204. Overexpression of TUG1 could suppress the inflammation in adipocytes via downregulating miR-204 and promote GLUT4/PPARγ/AKT pathway high-glucose-induced inflammation in 3T3-L1 cells. miR-204 inhibitors could also suppress high-glucose-induced inflammation in 3T3-L1 cells via promoting SIRT1/ GLUT4/PPARγ/AKT pathway. LncRNA TUG1 could negatively regulate miR-204 to alleviate inflammation and insulin tolerance via promoting SIRT1/GLUT4/PPARγ/AKT pathway.

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Data were available on request from the corresponding authors.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, China

    Ying Zhang & Mingyu Gu

  2. Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China

    Yuhang Ma & Yongde Peng

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  1. Ying Zhang
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  2. Mingyu Gu
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YP wrote the manuscript, YZ, MG conducted the experiments and collected the data, MG, YM collected and analyzed the data, YZ, YP designed the study, and all authors approved the submission.

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Correspondence to Yongde Peng.

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Zhang, Y., Gu, M., Ma, Y. et al. LncRNA TUG1 reduces inflammation and enhances insulin sensitivity in white adipose tissue by regulating miR-204/SIRT1 axis in obesity mice. Mol Cell Biochem 475, 171–183 (2020). https://doi.org/10.1007/s11010-020-03869-6

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  • DOI: https://doi.org/10.1007/s11010-020-03869-6

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