Depletion of HuR in murine skeletal muscle enhances exercise endurance and prevents cancer-induced muscle atrophy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA554451 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9678580.fastq.gz | Fastqsanger.gz | |||
| SRR9678581.fastq.gz | Fastqsanger.gz | |||
| SRR9678582.fastq.gz | Fastqsanger.gz | |||
| SRR9678575.fastq.gz | Fastqsanger.gz | |||
| SRR9678576.fastq.gz | Fastqsanger.gz |
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Project description:Here we show that, when compared to control mice, muscle specific HuR knockout (muHuR-KO) animals have higher exercise endurance that is associated with a significant increase in oxygen consumption and carbon dioxide production. Histological analysis demonstrates that the absence of HuR significantly enhances the proportion of oxidative type I fibers in several skeletal muscles, showing that under normal conditions, HuR promotes the formation of glycolytic type II fibers. HuR mediates this outcome by collaborating with the mRNA decay factor KSRP, to destabilize the PGC-1α mRNA, a well-known promoter of type I fiber formation. Furthermore, the type I fiber-enriched phenotype of muHuR-KO mice is associated with a protection against cancer cachexia-induced muscle wasting
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Project description:Enhancing exercise endurance holds significant practical implications for boosting the physical fitness of the general population to address daily challenges and improving the physical capabilities and quality of life of patients with relevant diseases. Polysaccharides from Gynostemma pentaphyllum Makino (GPMP) have been shown to increase the expression of slow muscle fibers in muscles. However, the underlying mechanism remains to be further investigated. Previous research has indicated that alterations in the gut microbiota are closely intertwined with the improvement of muscle endurance. In this study, we demonstrate that GPMP enriches B. acidifaciens in the murine gut, showing a notable association with muscle endurance. Subsequently, we identified that succinic acid, a key metabolite of B. acidifaciens, can effectively enhance the exercise endurance of mice and the antioxidant capacity of their muscles, protecting the muscles from damage induced by strenuous exercise. Specifically, succinic acid enters the circulatory system and acts upon skeletal muscles, activating the non-canonical Wnt signaling pathway. This activation leads to an increase in slow muscle fibers and an elevation of the oxidative phosphorylation level in muscle tissues, ultimately contributing to the improvement of exercise endurance. Moreover, we observed similar increases in B. acidifaciens and succinic acid in the feces and sera of endurance athletes. Overall, these findings uncover that GPMP modulates the body's exercise endurance through specific gut microbiota and their metabolites, thereby establishing a regulatory mechanism of host exercise endurance by gut microbiota.
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