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Demethylation of miR-299-5p by aerobic exercise relieves insulin resistance in the vascular endothelium by repressing resistin

  • Ying Cai
    Affiliations
    Department of Rehabilitation Medicine, Xiangya Hospital Central South University, Changsha 410008, P. R. China

    National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha 410008, P. R. China
    Search for articles by this author
  • Mingzhu Wang
    Affiliations
    Department of Rehabilitation Medicine, Xiangya Hospital Central South University, Changsha 410008, P. R. China

    National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha 410008, P. R. China
    Search for articles by this author
  • Yujiao Zong
    Affiliations
    Department of Rehabilitation Medicine, Xiangya Hospital Central South University, Changsha 410008, P. R. China

    National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha 410008, P. R. China
    Search for articles by this author
  • Cui Li
    Affiliations
    Department of Rehabilitation Medicine, Xiangya Hospital Central South University, Changsha 410008, P. R. China

    National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha 410008, P. R. China
    Search for articles by this author
  • Siqian Fu
    Affiliations
    Department of Rehabilitation Medicine, Xiangya Hospital Central South University, Changsha 410008, P. R. China

    National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha 410008, P. R. China
    Search for articles by this author
  • Kangling Xie
    Correspondence
    Corresponding author at: Department of Rehabilitation Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, No. 87, Xiangya Road, Changsha 410008, P. R. China.
    Affiliations
    Department of Rehabilitation Medicine, Xiangya Hospital Central South University, Changsha 410008, P. R. China

    National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha 410008, P. R. China
    Search for articles by this author
Published:November 21, 2022DOI:https://doi.org/10.1016/j.diabres.2022.110176

      Abstract

      Aims

      Insulin resistance (IR) is a critical marker underlying type 2 diabetes mellitus (T2DM). Exercise is reported to prevent IR, yet the mechanism of which is complicated and largely unknown. Here, the study aimed to ascertain whether and how aerobic exercise mediates IR in T2DM.

      Methods

      An in vivo model of high-fat diet (HFD)-induced IR and an in vitro model of high-glucose-induced IR were constructed.

      Results

      Aerobic exercise training in mice led to attenuation of IR in the vascular endothelium. microRNA-299-5p (miR-299-5p) expression was deficient in T2MD, which could be restored by aerobic exercise through modulating the DNA methylation modification enzymes. The expression of miR-299-5p enhanced by aerobic exercise consequently resulted in ameliorating the IR in vivo. Furthermore, increased levels of nitric oxide (NO), reduced levels of Angiotensin II (Ang II), vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) in response to miR-299-5p elevation suggested the anti-IR role of miR-299-5p in IR-cell model. Dual-luciferase reporter and ChIP assays identified that miR-299-5p could bind to resistin and hence repressed the resistin level.

      Conclusion

      The key observation of the study is that aerobic exercise stimulates miR-299-5p-targeted resistin inhibition through demethylation, which underlies the mechanism of reducing IR.

      Keywords

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