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author:

Cong, Chen (Cong, Chen.) [1] | Jiang, Cai (Jiang, Cai.) [2] | Lin, Ting (Lin, Ting.) [3] | Hu, Yue (Hu, Yue.) [4] | Wu, Huijuan (Wu, Huijuan.) [5] | Xiang, Qing (Xiang, Qing.) [6] | Yang, Minguang (Yang, Minguang.) [7] | Wang, Sinuo (Wang, Sinuo.) [8] | Han, Xiao (Han, Xiao.) [9] (Scholars:韩霄) | Tao, Jing (Tao, Jing.) [10]

Indexed by:

Scopus SCIE

Abstract:

Aim: Type 2 diabetes mellitus (T2DM) is one of the most common diseases, and epigenetic modification N6-methyladenosine (m(6)A) is essential for transcriptional modulation involved in its development. However, the precise role and landscape of transcriptome-wide m(6)A alterations in molecular adaptations after physical exercise have yet to be fully elucidated. Methods: Four-week-old male C57BL/6J mice received a high-fat diet (HFD) for 12 weeks to establish a diabetic state, and HFD mice were simultaneously subjected to physical exercise (HFD + EX). The hepatic RNA m(6)A methylome was examined, the conjoint MeRIP-seq and RNA-seq was performed, and the exercise-modulated genes were confirmed. Results: Physical exercise significantly ameliorates liver metabolic disorder and triggers a dynamic change in hepatic RNA m(6)A. By analyzing the distribution of m(6)A in transcriptomes, an abundance of m(6)A throughout mRNA transcripts and a pattern of conserved m(6)A after physical exercise was identified. It is noteworthy that conjoint MeRIP-seq and RNA-seq data revealed that both differentially methylated genes and differentially expressed genes were enriched in all stages of the PI3K-Akt signaling pathway, in particular the upstream nodes of this pathway, which are considered a valuable therapeutic target for T2DM. Moreover, in vivo and in vitro analyses showed that exercise-mediated methyltransferase Rbm15 positively regulated the expression of two upstream genes (Itga3 and Fgf21) in an m(6)A-dependent manner. Conclusion: These findings highlight the pivotal role of the exercise-induced m(6)A epigenetic network and contribute insights into the intricate epigenetic mechanism underlying insulin signaling.

Keyword:

PI3K-Akt signaling RNA m(6)A modification transcriptome type 2 diabetes mellitus

Community:

  • [ 1 ] [Cong, Chen]Fujian Univ Tradit Chinese Med, Rehabil Ind Inst, Fuzhou 350122, Fujian, Peoples R China
  • [ 2 ] [Jiang, Cai]Fujian Univ Tradit Chinese Med, Rehabil Ind Inst, Fuzhou 350122, Fujian, Peoples R China
  • [ 3 ] [Hu, Yue]Fujian Univ Tradit Chinese Med, Rehabil Ind Inst, Fuzhou 350122, Fujian, Peoples R China
  • [ 4 ] [Wu, Huijuan]Fujian Univ Tradit Chinese Med, Rehabil Ind Inst, Fuzhou 350122, Fujian, Peoples R China
  • [ 5 ] [Xiang, Qing]Fujian Univ Tradit Chinese Med, Rehabil Ind Inst, Fuzhou 350122, Fujian, Peoples R China
  • [ 6 ] [Yang, Minguang]Fujian Univ Tradit Chinese Med, Rehabil Ind Inst, Fuzhou 350122, Fujian, Peoples R China
  • [ 7 ] [Wang, Sinuo]Fujian Univ Tradit Chinese Med, Rehabil Ind Inst, Fuzhou 350122, Fujian, Peoples R China
  • [ 8 ] [Tao, Jing]Fujian Univ Tradit Chinese Med, Rehabil Ind Inst, Fuzhou 350122, Fujian, Peoples R China
  • [ 9 ] [Cong, Chen]Fujian Univ Tradit Chinese Med, Natl Local Joint Engn Res Ctr Rehabil Med Technol, Fuzhou, Fujian, Peoples R China
  • [ 10 ] [Xiang, Qing]Fujian Univ Tradit Chinese Med, Natl Local Joint Engn Res Ctr Rehabil Med Technol, Fuzhou, Fujian, Peoples R China
  • [ 11 ] [Yang, Minguang]Fujian Univ Tradit Chinese Med, Natl Local Joint Engn Res Ctr Rehabil Med Technol, Fuzhou, Fujian, Peoples R China
  • [ 12 ] [Tao, Jing]Fujian Univ Tradit Chinese Med, Natl Local Joint Engn Res Ctr Rehabil Med Technol, Fuzhou, Fujian, Peoples R China
  • [ 13 ] [Cong, Chen]Fujian Univ Tradit Chinese Med, Fujian Key Lab cognit Rehabil, Fuzhou, Fujian, Peoples R China
  • [ 14 ] [Xiang, Qing]Fujian Univ Tradit Chinese Med, Fujian Key Lab cognit Rehabil, Fuzhou, Fujian, Peoples R China
  • [ 15 ] [Yang, Minguang]Fujian Univ Tradit Chinese Med, Fujian Key Lab cognit Rehabil, Fuzhou, Fujian, Peoples R China
  • [ 16 ] [Tao, Jing]Fujian Univ Tradit Chinese Med, Fujian Key Lab cognit Rehabil, Fuzhou, Fujian, Peoples R China
  • [ 17 ] [Cong, Chen]Fujian Univ Tradit Chinese Med, Coll Rehabil Med, Fuzhou, Fujian, Peoples R China
  • [ 18 ] [Jiang, Cai]Fujian Univ Tradit Chinese Med, Coll Rehabil Med, Fuzhou, Fujian, Peoples R China
  • [ 19 ] [Hu, Yue]Fujian Univ Tradit Chinese Med, Coll Rehabil Med, Fuzhou, Fujian, Peoples R China
  • [ 20 ] [Wu, Huijuan]Fujian Univ Tradit Chinese Med, Coll Rehabil Med, Fuzhou, Fujian, Peoples R China
  • [ 21 ] [Xiang, Qing]Fujian Univ Tradit Chinese Med, Coll Rehabil Med, Fuzhou, Fujian, Peoples R China
  • [ 22 ] [Yang, Minguang]Fujian Univ Tradit Chinese Med, Coll Rehabil Med, Fuzhou, Fujian, Peoples R China
  • [ 23 ] [Wang, Sinuo]Fujian Univ Tradit Chinese Med, Coll Rehabil Med, Fuzhou, Fujian, Peoples R China
  • [ 24 ] [Tao, Jing]Fujian Univ Tradit Chinese Med, Coll Rehabil Med, Fuzhou, Fujian, Peoples R China
  • [ 25 ] [Lin, Ting]Fujian Med Univ, Mengchao Hepatobil Hosp, Fuzhou 350025, Fujian, Peoples R China
  • [ 26 ] [Han, Xiao]Fuzhou Univ, Coll Biol Sci & Engn, Fuzhou, Fujian, Peoples R China
  • [ 27 ] [Han, Xiao]Fujian Univ Tradit Chinese Med, Inst Rehabil Ind, Fuzhou 350122, Fujian, Peoples R China

Reprint 's Address:

  • 韩霄

    [Tao, Jing]Fujian Univ Tradit Chinese Med, Rehabil Ind Inst, Fuzhou 350122, Fujian, Peoples R China;;[Tao, Jing]Fujian Univ Tradit Chinese Med, Natl Local Joint Engn Res Ctr Rehabil Med Technol, Fuzhou, Fujian, Peoples R China;;[Tao, Jing]Fujian Univ Tradit Chinese Med, Fujian Key Lab cognit Rehabil, Fuzhou, Fujian, Peoples R China;;[Tao, Jing]Fujian Univ Tradit Chinese Med, Coll Rehabil Med, Fuzhou, Fujian, Peoples R China;;[Han, Xiao]Fuzhou Univ, Coll Biol Sci & Engn, Fuzhou, Fujian, Peoples R China

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Source :

ACTA PHYSIOLOGICA

ISSN: 1748-1708

Year: 2024

Issue: 6

Volume: 240

5 . 6 0 0

JCR@2023

Cited Count:

WoS CC Cited Count: 2

SCOPUS Cited Count: 1

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 0

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