lncRNA TUG1 promotes the brown remodeling of white adipose tissue by regulating miR‑204‑targeted SIRT1 in diabetic mice

Zhang,Ying; Ma,Yuhang; Gu,Mingyu; Peng,Yongde

doi:10.3892/ijmm.2020.4741

lncRNA TUG1 promotes the brown remodeling of white adipose tissue by regulating miR‑204‑targeted SIRT1 in diabetic mice

Authors:
- Ying Zhang
- Yuhang Ma
- Mingyu Gu
- Yongde Peng
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Affiliations: Department of Endocrinology and Metabolism, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, P.R. China, Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, P.R. China
Published online on: September 28, 2020 https://doi.org/10.3892/ijmm.2020.4741
Pages: 2225-2234

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Abstract

The present study aimed to explore the mechanisms of the long non‑coding RNA TUG/miR‑204/SIRT1 axis in the pathogenesis of obesity. For this purpose, a diabetic mouse model was constructed using a high‑fat diet and streptozocin, and the mice were treated with TUG1 virus via tail intravenous injection. Body weight, serum glucose levels, insulin levels and testicular fat, as well as the expression levels of TUG1, miR‑204, Sirtuin 1 (SIRT1) and the AMP‑activated protein kinase (AMPK)/acetyl‑CoA carboxylase (ACC) signaling pathway were detected. Furthermore, the regulatory mechanisms of TUG1/SIRT1 and miR‑204 in the development of diabetes were also explored. The results revealed that the overexpression of TUG1 significantly attenuated body weight, serum glucose levels, insulin tolerance and fatty accumulation in diabetic mice. Furthermore, the overexpression of TUG1 significantly increased the expression SIRT1, adipose triglyceride lipase (ATGL), peroxisome proliferator‑activated receptor α (PPARα), peroxisome proliferator‑activated receptor gamma coactivator 1‑α (PGC‑1α) and uncoupling protein‑1 (UCP‑1), as well as the phosphorylation levels of AMPK and ACC, and decreased the expression of miR‑204 in adipose tissues and 3T3‑L1 cells. miR‑204 inhibitor increased the expression SIRT1, ATGL, PPARα, PGC‑1α and UCP‑1, as well as the phosphorylation levels of AMPK and ACC, and decreased the expression of miR‑204 in the 3T3‑L1 cells; however, the silencing of SIRT1 attenuated these effects. On the whole, the findings of the present study demonstrate that lncRNA TUG1 significantly reverses the development of diabetes by downregulating the expression of miR‑204, and upregulating its targeted SIRT1/AMPK/ACC signaling pathway.

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