Demethylation of miR-299-5p by aerobic exercise relieves insulin resistance in the vascular endothelium by repressing resistin
Demethylation of miR-299-5p by aerobic exercise relieves insulin resistance in the vascular endothelium by repressing resistin
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DOI：
10.1016/j.diabres.2022.110176
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发表时间：
2022-12-10
影响因子：
5.1
通讯作者：
Xie，Kangling
中科院分区：
文献类型：
--
作者：
Cai，Ying;Wang，Mingzhu;Xie，Kangling
AimsInsulin 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.MethodsAn in vivo model of high-fat diet (HFD)-induced IR and an in vitro model of high-glucose-induced IR were constructed.ResultsAerobic 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.ConclusionThe 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.
