Bulletin of the National Research Centre (Dec 2023)

In vitro mitochondrial and myogenic gene expression is influenced by formoterol in human myotubes

  • Emily L. Zumbro,
  • Anthony A. Duplanty,
  • Ryan A. Gordon,
  • Gena D. Guerin,
  • Matthew F. Brisebois,
  • Matthew L. Sokoloski,
  • Brandon R. Rigby

DOI
https://doi.org/10.1186/s42269-023-01154-2
Journal volume & issue
Vol. 47, no. 1
pp. 1 – 12

Abstract

Read online

Abstract Background Exercise is an effective treatment for establishing and maintaining skeletal muscle health. The interconnected cascade of gene expression pathways related to myogenesis, mitochondrial homeostasis, and thyroid hormone metabolism are critical to skeletal muscle health. This in vitro study was conducted to investigate the effects of exercise mimetic (formoterol) stimulation on human skeletal muscle cell signaling during myogenesis, and to provide insight on potential targets for future studies exploring therapies for skeletal muscle atrophy. Human myoblasts were cultured and differentiated to evaluate the effects of exercise mimetic stimulation on gene expression during mid and late myogenesis. Results We characterized the expression of 24 genes related to myogenesis, mitochondrial biogenesis, thyroid hormone metabolism, and cellular homeostasis and found that 21 genes were altered in response to formoterol, thus affecting related skeletal muscle pathways. Additionally, formoterol stimulation resulted in a myogenic program that appears to favor prolonged myoblast proliferation and delayed myotube maturation. Robust, yet distinctive effects of exercise mimetic stimulation on gene expression during mid-myogenesis and at terminal differentiation occurred. For instance, MYF5 increased in D6 FORM compared to other groups (p < 0.001) while MYOD and MYOG both decreased expression in the FORM groups compared to CON (p < 0.01). Secondly, mitochondrial biogenesis genes were stimulated following formoterol administration, namely PGC-1α, PGC-1β, and TFAM (p < 0.05). Uniquely in our study, thyroid hormone metabolism related genes were differentially expressed. For instance, DIO2 and DIO3 were both stimulated following formoterol administration (p < 0.05). Conclusions The results of our study support the groundwork for establishing further experiments utilizing exercise signaling as a clinical treatment in models targeting dysfunctional skeletal muscle cell growth.

Keywords