Abstract
Many of the molecular and cellular mechanisms discovered to regulate skeletal muscle hypertrophy were first identified using the rodent synergist ablation model. This model reveals the intrinsic capability and necessary pathways of skeletal muscle growth in response to mechanical overload (MOV). Reminiscent of the rapid cellular growth observed with cancer, we hypothesized that in response to MOV, skeletal muscle would undergo metabolic programming to sustain increased demands to support hypertrophy. To test this hypothesis, we analyzed the gene expression of specific metabolic pathways taken from transcriptomic microarray data of a MOV time course. We found an upregulation of genes involved in the oxidative branch of the pentose phosphate pathways (PPP) and mitochondrial branch of the folate cycle suggesting an increase in the production of NADPH. In addition, we sought to determine the potential role of skeletal muscle-enriched microRNA (myomiRs) and satellite cells in the regulation of the metabolic pathways that changed during MOV. We observed an inverse pattern in gene expression between muscle-enriched myomiR-1 and its known target gene glucose-6-phosphate dehydrogenase, G6pdx, suggesting myomiR regulation of PPP activation in response to MOV. Satellite cell fusion had a significant but modest impact on PPP gene expression. These transcriptomic findings suggest the robust muscle hypertrophy induced by MOV requires enhanced redox metabolism via PPP production of NADPH which is potentially regulated by a myomiR network.
Document Type
Article
Publication Date
12-9-2021
Digital Object Identifier (DOI)
https://doi.org/10.14814/phy2.15137
Funding Information
This work was supported by funding from the NIH National Institute of General Medical Sciences (grant no. P20GM104320- 07) to IJV.
Repository Citation
Valentino, Taylor; Figueiredo, Vandre C.; Mobley, C. Brooks; McCarthy, John J.; and Vechetti, Ivan J. Jr., "Evidence of MyomiR Regulation of the Pentose Phosphate Pathway during Mechanical Load-Induced Hypertrophy" (2021). Physiology Faculty Publications. 186.
https://uknowledge.uky.edu/physiology_facpub/186
Supporting information: Fig S1-S4
Notes/Citation Information
Published in Physiological Reports, v. 9, issue 23, e15137.
© 2021 The Authors
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.