ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2023
Innately expressed estrogen-related receptors in the skeletal muscle are indispensable for exercise fitness.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Skeletal muscle reprogramming of metabolic, ribosomal and developmental pathways contributes to Roux-en-Y gastric bypass-induced adaptation in women.EBioMedicine · 2026Article
- Emerging evidence for skeletal muscle as a target of BPA exposure.BMC endocrine disorders · 2026Review
- Structural Pharmacology of Estrogen-Related Receptors.ACS pharmacology & translational science · 2026Review
- Cold exposure induces the constitutively active thermogenic receptor, GPR3, via ERRα and ERRγ.Molecular metabolism · 2026Article
- Estrogen-Related Receptor Alpha Promotes Skeletal Muscle Regeneration and Mitigates Muscular Dystrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Signaling networks governing skeletal muscle growth, atrophy, and cachexiaSkeletal muscle · 2025Review
- The AMPK Pathway: Molecular Rejuvenation of Metabolism and Mitochondria.Annual review of cell and developmental biology · 2025Review
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Estrogen-related receptors regulate innate and adaptive muscle mitochondrial energetics through cooperative and distinct actions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Oestrogen Receptor Alpha in Myocyte Maintains Muscle Regeneration in Duchenne Muscular Dystrophy.Journal of cachexia, sarcopenia and muscle · 2025Article
- A 6-Minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models.JACC. Basic to translational science · 2025Article
- The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy through TFEB.Molecular pharmacology · 2024Article
- Estrogen-Related Receptor α: A Key Transcription Factor in the Regulation of Energy Metabolism at an Organismic Level and a Target of the ABA/LANCL Hormone Receptor System.International journal of molecular sciences · 2024Review
- A 6-minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models.bioRxiv : the preprint server for biology · 2024Article
- Single-Nuclei RNA-Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease.Circulation research · 2023Article
- Review
- Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity.ACS chemical biology · 2023Article
- Exercise and Ischemia-Activated Pathways in Limb Muscle Angiogenesis and Vascular Regeneration.Methodist DeBakey cardiovascular journal · 2023Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
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Abstract
Transcriptional determinants in the skeletal muscle that govern exercise capacity, while poorly defined, could provide molecular insights into how exercise improves fitness. Here, we have elucidated the role of nuclear receptors, estrogen-related receptor alpha and gamma (ERRα/γ) in regulating myofibrillar composition, contractility, and exercise capacity in skeletal muscle. We used muscle-specific single or double (DKO) ERRα/γ knockout mice to investigate the effect of ERRα/γ deletion on muscle and exercise parameters. Individual knockout of ERRα/γ did not have a significant impact on the skeletal muscle. On the other hand, DKO mice exhibit pale muscles compared to wild-type (WT) littermates. RNA-seq analysis revealed a predominant decrease in expression of genes linked to mitochondrial and oxidative metabolism in DKO versus WT muscles. DKO muscles exhibit marked repression of oxidative enzymatic capacity, as well as mitochondrial number and size compared to WT muscles. Mitochondrial function is also impaired in single myofibers isolated from DKO versus WT muscles. In addition, mutant muscles exhibit reduced angiogenic gene expression and decreased capillarity. Consequently, DKO mice have a significantly reduced exercise capacity, further reflected in poor fatigue resistance of DKO mice in in vivo contraction assays. These results show that ERRα and ERRγ together are a critical link between muscle aerobic capacity and exercise tolerance. The ERRα/γ mutant mice could be valuable for understanding the long-term impact of impaired mitochondria and vascular supply on the pathogenesis of muscle-linked disorders.
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Registered trials
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