Charles Darwin University

CDU eSpace
Institutional Repository

 
CDU Staff and Student only
 

Multi-Omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in type 2 diabetic obesity

Rowlands, David, Page, Rachel, Sukala, William, Giri, Mamta, Ghimbovschi, Svetlana, Hayat, Irum, Cheema, Birinder, Lys, Isabelle, Leikis, Murray, Sheard, Phillip, Wakefield, St. John, Breier, Bernhard, Hathout, Yetrib, Brown, Kristy, Marathi, Ramya, Orkunoglu-Suer, Funda E., Devaney, Joseph, Leiken, Benjamin, Many, Gina, Krebs, Jeremy, Hopkins, Will G. and Hoffman, Eric P. (2014). Multi-Omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in type 2 diabetic obesity. Physiological Genomics,46(20):747-765.

Document type: Journal Article
Citation counts: Altmetric Score Altmetric Score is 5
Google Scholar Search Google Scholar

IRMA ID 75039815xPUB558
Title Multi-Omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in type 2 diabetic obesity
Author Rowlands, David
Page, Rachel
Sukala, William
Giri, Mamta
Ghimbovschi, Svetlana
Hayat, Irum
Cheema, Birinder
Lys, Isabelle
Leikis, Murray
Sheard, Phillip
Wakefield, St. John
Breier, Bernhard
Hathout, Yetrib
Brown, Kristy
Marathi, Ramya
Orkunoglu-Suer, Funda E.
Devaney, Joseph
Leiken, Benjamin
Many, Gina
Krebs, Jeremy
Hopkins, Will G.
Hoffman, Eric P.
Journal Name Physiological Genomics
Publication Date 2014
Volume Number 46
Issue Number 20
ISSN 1094-8341   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-84907970598
Start Page 747
End Page 765
Total Pages 19
Place of Publication United States
Publisher American Physiological Society
HERDC Category C1 - Journal Article (DIISR)
Abstract Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silencing by miRNAs are potential environmental modulators of skeletal muscle plasticity to chronic exercise in healthy and diseased populations. We utilized transcriptome networks to connect exercise-induced differential methylation and miRNA with functional skeletal muscle plasticity. Biopsies of the vastus lateralis were collected from middle-aged Polynesian men and women with morbid obesity (44 kg/m2 ± 10) and Type 2 diabetes before and following 16 wk of resistance (n = 9) or endurance training (n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses were obtained via microarray, filtered by novel effect-size based false discovery rate probe selection preceding bioinformatic interrogation. Metabolic and microvascular transcriptome topology dominated the network landscape following endurance exercise. Lipid and glucose metabolism modules were connected to: microRNA (miR)-29a; promoter region hypomethylation of nuclear receptor factor (NRF1) and fatty acid transporter (SLC27A4), and hypermethylation of fatty acid synthase, and to exon hypomethylation of 6-phosphofructo-2-kinase and Ser/Thr protein kinase. Directional change in the endurance networks was validated by lower intramyocellular lipid, increased capillarity, GLUT4, hexokinase, and mitochondrial enzyme activity and proteome. Resistance training also lowered lipid and increased enzyme activity and caused GLUT4 promoter hypomethylation; however, training was inconsequential to GLUT4, capillarity, and metabolic transcriptome. miR-195 connected to negative regulation of vascular development. To conclude, integrated molecular network modelling revealed differential DNA methylation and miRNA expression changes occur in skeletal muscle in response to chronic exercise training that are most pronounced with endurance training and topographically associated with functional metabolic and microvascular plasticity relevant to diabetes rehabilitation.
DOI http://dx.doi.org/10.1152/physiolgenomics.00024.2014   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
 
Versions
Version Filter Type
Access Statistics: 24 Abstract Views  -  Detailed Statistics
Created: Wed, 19 Aug 2015, 12:18:09 CST