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Article

Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway

  • Authors:
    • Shuzhi Zhao
    • Jun Li
    • Na Wang
    • Bingqing Zheng
    • Tao Li
    • Qing Gu
    • Xun Xu
    • Zhi Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, First People's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai 200080, P.R. China, Department of Ophthalmology, Lishui City Center Hospital, Lishui, Zhejiang 323000, P.R. China
  • Pages: 6112-6118
    |
    Published online on: July 31, 2015
       https://doi.org/10.3892/mmr.2015.4164
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Abstract

Inflammation is a major contributing factor in the development of diabetic microvascular complications, regardless of whether improved glycaemic control is achieved. Studies have increasingly indicated that fenofibrate, a lipid‑lowering therapeutic agent in clinical use, exerts a potential anti‑inflammatory effect, which is mediated by sirtuin 1 (SIRT1; an NAD+‑dependent deacetylase) in endothelial cells. The aim of the present study was to investigate the inhibitory effect of fenofibrate on metabolic memory (via the regulation of SIRT1), and inflammatory responses in cell and animal models of diabetic retinopathy (DR). The data demonstrated that high glucose treatment in human retinal endothelial cells (HRECs) inhibited the expression and deacetylase activity of SIRT1. The reduction of SIRT1 expression and deacetylase activity persisted following a return to normal glucose levels. Furthermore, nuclear factor‑κB expression was observed to be negatively correlated with SIRT1 expression and activity in HRECs under high glucose levels and the subsequent return to normal glucose levels. Fenofibrate treatment abrogated these changes. Knockdown of SIRT1 attenuated the effect of fenofibrate on high glucose‑induced NF‑κB expression. In addition, fenofibrate upregulated SIRT1 expression through peroxisome proliferator‑activated receptor α in high glucose‑induced metabolic memory. These findings indicate that fenofibrate is important in anti‑inflammatory processes and suppresses the cellular metabolic memory of high glucose‑induced stress via the SIRT1‑dependent signalling pathway. Thus, treatment with fenofibrate may offer a promising therapeutic strategy for halting the development of DR and other complications of diabetes.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao S, Li J, Wang N, Zheng B, Li T, Gu Q, Xu X and Zheng Z: Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway. Mol Med Rep 12: 6112-6118, 2015.
APA
Zhao, S., Li, J., Wang, N., Zheng, B., Li, T., Gu, Q. ... Zheng, Z. (2015). Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway. Molecular Medicine Reports, 12, 6112-6118. https://doi.org/10.3892/mmr.2015.4164
MLA
Zhao, S., Li, J., Wang, N., Zheng, B., Li, T., Gu, Q., Xu, X., Zheng, Z."Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway". Molecular Medicine Reports 12.4 (2015): 6112-6118.
Chicago
Zhao, S., Li, J., Wang, N., Zheng, B., Li, T., Gu, Q., Xu, X., Zheng, Z."Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway". Molecular Medicine Reports 12, no. 4 (2015): 6112-6118. https://doi.org/10.3892/mmr.2015.4164
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao S, Li J, Wang N, Zheng B, Li T, Gu Q, Xu X and Zheng Z: Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway. Mol Med Rep 12: 6112-6118, 2015.
APA
Zhao, S., Li, J., Wang, N., Zheng, B., Li, T., Gu, Q. ... Zheng, Z. (2015). Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway. Molecular Medicine Reports, 12, 6112-6118. https://doi.org/10.3892/mmr.2015.4164
MLA
Zhao, S., Li, J., Wang, N., Zheng, B., Li, T., Gu, Q., Xu, X., Zheng, Z."Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway". Molecular Medicine Reports 12.4 (2015): 6112-6118.
Chicago
Zhao, S., Li, J., Wang, N., Zheng, B., Li, T., Gu, Q., Xu, X., Zheng, Z."Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway". Molecular Medicine Reports 12, no. 4 (2015): 6112-6118. https://doi.org/10.3892/mmr.2015.4164
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