Dataset Information

Applying exercise-mimetic engineered skeletal muscle model to interrogate the adaptive response of irisin to mechanical force.

ABSTRACT: Physical exercise induces the secretion of irisin from contractile muscle into circulation; however, the adaptive response of irisin to mechanical stimulus in skeletal muscle in vitro remains numerously unknown. In an effort to investigate whether irisin is inducible in vitro, we developed a bioreactor consisting of a retractable mechanical force controller and a conditional tissue culture system. Upon this model, a distinguished surge of irisin was detected in stretched myotubes as cyclic strain initiated, and the surge was able to be stalled by knocking out FNDC5. Intriguingly, increased irisin secretory is associated with the shifts of MyHC isoforms from anaerobic type to aerobic type in myotubes. We further revealed that PGC-1α1 and PGC-1α4 mRNAs expression, rather than PGC-1α2 and PGC-1α3, contributed to the generation of irisin in myotubes during cyclic strain. Lastly, combined with co-culturing MC3T3 osteoblasts, we demonstrated the bioactivity of generated irisin, promoting the osteogenic differentiation.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9010619 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Applying exercise-mimetic engineered skeletal muscle model to interrogate the adaptive response of irisin to mechanical force.

Zhang Yuwei Y Wang Lizhen L Kang Hongyan H Lin Chia-Ying CY Fan Yubo Y

iScience 20220323 4

Physical exercise induces the secretion of irisin from contractile muscle into circulation; however, the adaptive response of irisin to mechanical stimulus in skeletal muscle <i>in vitro</i> remains numerously unknown. In an effort to investigate whether irisin is inducible <i>in vitro</i>, we developed a bioreactor consisting of a retractable mechanical force controller and a conditional tissue culture system. Upon this model, a distinguished surge of irisin was detected in stretched myotubes a ...[more]

PMID: 35434556

Similar Datasets

Project description:Background: Desmin is a muscle-specific protein belonging to the intermediate filament family. Desmin mutations are linked to skeletal muscle defects, including inherited myopathies with severe clinical manifestations. The aim of this study was to examine the role of desmin in skeletal muscle remodeling and performance gain induced by muscle mechanical overloading which mimics resistance training. Methods: Plantaris muscles were overloaded by surgical ablation of gastrocnemius and soleus muscles. The functional response of plantaris muscle to mechanical overloading in desmin-deficient mice (DesKO, n = 32) was compared to that of control mice (n = 36) after 7-days or 1-month overloading. To elucidate the molecular mechanisms implicated in the observed partial adaptive response of DesKO muscle, we examined the expression levels of genes involved in muscle growth, myogenesis, inflammation and oxidative energetic metabolism. Moreover, ultrastructure and the proteolysis pathway were explored. Results: Contrary to control, absolute maximal force did not increase in DesKO muscle following 1-month mechanical overloading. Fatigue resistance was also less increased in DesKO as compared to control muscle. Despite impaired functional adaptive response of DesKO mice to mechanical overloading, muscle weight and the number of oxidative MHC2a-positive fibers per cross-section similarly increased in both genotypes after 1-month overloading. However, mechanical overloading-elicited remodeling failed to activate a normal myogenic program after 7-days overloading, resulting in proportionally reduced activation and differentiation of muscle stem cells. Ultrastructural analysis of the plantaris muscle after 1-month overloading revealed muscle fiber damage in DesKO, as indicated by the loss of sarcomere integrity and mitochondrial abnormalities. Moreover, the observed accumulation of autophagosomes and lysosomes in DesKO muscle fibers could indicate a blockage of autophagy. To address this issue, two main proteolysis pathways, the ubiquitin-proteasome system and autophagy, were explored in DesKO and control muscle. Our results suggested an alteration of proteolysis pathways in DesKO muscle in response to mechanical overloading. Conclusion: Taken together, our results show that mechanical overloading increases the negative impact of the lack of desmin on myofibril organization and mitochondria. Furthermore, our results suggest that under these conditions, the repairing activity of autophagy is disturbed. Consequently, force generation is not improved despite muscle growth, suggesting that desmin is required for a complete response to resistance training in skeletal muscle.

Dataset Information

Applying exercise-mimetic engineered skeletal muscle model to interrogate the adaptive response of irisin to mechanical force.

Publications

Applying exercise-mimetic engineered skeletal muscle model to interrogate the adaptive response of irisin to mechanical force.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets