PMID- 36427628
OWN - NLM
STAT- MEDLINE
DCOM- 20230210
LR  - 20230210
IS  - 1872-8227 (Electronic)
IS  - 0168-8227 (Linking)
VI  - 195
DP  - 2023 Jan
TI  - Demethylation of miR-299-5p by aerobic exercise relieves insulin resistance in 
      the vascular endothelium by repressing resistin.
PG  - 110176
LID - S0168-8227(22)00990-1 [pii]
LID - 10.1016/j.diabres.2022.110176 [doi]
AB  - 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-alpha), 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.
CI  - Copyright (c) 2022. Published by Elsevier B.V.
FAU - Cai, Ying
AU  - Cai Y
AD  - Department of Rehabilitation Medicine, Xiangya Hospital Central South University, 
      Changsha 410008, PR China; National Clinical Research Center for Geriatric 
      Disorders, Xiangya Hospital Central South University, Changsha 410008, PR China.
FAU - Wang, Mingzhu
AU  - Wang M
AD  - Department of Rehabilitation Medicine, Xiangya Hospital Central South University, 
      Changsha 410008, PR China; National Clinical Research Center for Geriatric 
      Disorders, Xiangya Hospital Central South University, Changsha 410008, PR China.
FAU - Zong, Yujiao
AU  - Zong Y
AD  - Department of Rehabilitation Medicine, Xiangya Hospital Central South University, 
      Changsha 410008, PR China; National Clinical Research Center for Geriatric 
      Disorders, Xiangya Hospital Central South University, Changsha 410008, PR China.
FAU - Li, Cui
AU  - Li C
AD  - Department of Rehabilitation Medicine, Xiangya Hospital Central South University, 
      Changsha 410008, PR China; National Clinical Research Center for Geriatric 
      Disorders, Xiangya Hospital Central South University, Changsha 410008, PR China.
FAU - Fu, Siqian
AU  - Fu S
AD  - Department of Rehabilitation Medicine, Xiangya Hospital Central South University, 
      Changsha 410008, PR China; National Clinical Research Center for Geriatric 
      Disorders, Xiangya Hospital Central South University, Changsha 410008, PR China.
FAU - Xie, Kangling
AU  - Xie K
AD  - Department of Rehabilitation Medicine, Xiangya Hospital Central South University, 
      Changsha 410008, PR China; National Clinical Research Center for Geriatric 
      Disorders, Xiangya Hospital Central South University, Changsha 410008, PR China. 
      Electronic address: xyklx2020@163.com.
LA  - eng
PT  - Journal Article
DEP - 20221124
PL  - Ireland
TA  - Diabetes Res Clin Pract
JT  - Diabetes research and clinical practice
JID - 8508335
RN  - 0 (MicroRNAs)
RN  - 0 (Resistin)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Insulin Resistance/genetics
MH  - *MicroRNAs/metabolism
MH  - *Diabetes Mellitus, Type 2/genetics/therapy/metabolism
MH  - Resistin/genetics/metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - Endothelium, Vascular/metabolism
MH  - Demethylation
OTO - NOTNLM
OT  - Aerobic exercise
OT  - DNA methylation
OT  - Insulin resistance
OT  - MicroRNA-299-5p
OT  - Resistin
OT  - Vascular endothelial cells
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/11/26 06:00
MHDA- 2023/02/11 06:00
CRDT- 2022/11/25 19:24
PHST- 2022/08/15 00:00 [received]
PHST- 2022/10/13 00:00 [revised]
PHST- 2022/11/16 00:00 [accepted]
PHST- 2022/11/26 06:00 [pubmed]
PHST- 2023/02/11 06:00 [medline]
PHST- 2022/11/25 19:24 [entrez]
AID - S0168-8227(22)00990-1 [pii]
AID - 10.1016/j.diabres.2022.110176 [doi]
PST - ppublish
SO  - Diabetes Res Clin Pract. 2023 Jan;195:110176. doi: 10.1016/j.diabres.2022.110176. 
      Epub 2022 Nov 24.