ArticleMolecular metabolism2023
Loss of skeletal muscle estrogen-related receptors leads to severe exercise intolerance.
Article in Molecular metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Mitochondrial membrane lipid cardiolipin controls fiber-type adaptations in aging muscle via estrogen-related receptor γ.Nature aging · 2026Article
- Exercise pills for cardiometabolic health cannot mimic the exercise milieu.Trends in endocrinology and metabolism: TEM · 2026Review
- A novel PAAoptosis-inducing ERRα-targeting compound for combating hematopoietic and solid cancers.Cell death discovery · 2026Article
- 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
- Genetics-nutrition interactions control diurnal enhancer-promoter dynamics and liver lipid metabolism.Cell metabolism · 2025Article
- 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
- Network-based modelling reveals cell-type enriched patterns of non-coding RNA regulation during human skeletal muscle remodelling.bioRxiv : the preprint server for biology · 2024Article
- Network-based modelling reveals cell-type enriched patterns of non-coding RNA regulation during human skeletal muscle remodelling.NAR molecular medicine · 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
- The potential of therapeutic strategies targeting mitochondrial biogenesis for the treatment of insulin resistance and type 2 diabetes mellitus.Archives of pharmacal research · 2024Review
- The Acute, Short-, and Long-Term Effects of Endurance Exercise on Skeletal Muscle Transcriptome Profiles.International journal of molecular sciences · 2024Article
- Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveSkeletal muscle oxidative capacity is central to physical activity, exercise capacity and whole-body metabolism. The three estrogen-related receptors (ERRs) are regulators of oxidative metabolism in many cell types, yet their roles in skeletal muscle remain unclear. The main aim of this study was to compare the relative contributions of ERRs to oxidative capacity in glycolytic and oxidative muscle, and to determine defects associated with loss of skeletal muscle ERR function.
methodsWe assessed ERR expression, generated mice lacking one or two ERRs specifically in skeletal muscle and compared the effects of ERR loss on the transcriptomes of EDL (predominantly glycolytic) and soleus (oxidative) muscles. We also determined the consequences of the loss of ERRs for exercise capacity and energy metabolism in mice with the most severe loss of ERR activity.
resultsERRs were induced in human skeletal muscle in response to an exercise bout. Mice lacking both ERRα and ERRγ (ERRα/γ dmKO) had the broadest and most dramatic disruption in skeletal muscle gene expression. The most affected pathway was "mitochondrial function", in particular Oxphos and TCA cycle genes, and transcriptional defects were more pronounced in the glycolytic EDL than the oxidative soleus. Mice lacking ERRβ and ERRγ, the two isoforms expressed highly in oxidative muscles, also exhibited defects in lipid and branch chain amino acid metabolism genes, specifically in the soleus. The pronounced disruption of oxidative metabolism in ERRα/γ dmKO mice led to pale muscles, decreased oxidative capacity, histochemical patterns reminiscent of minicore myopathies, and severe exercise intolerance, with the dmKO mice unable to switch to lipid utilization upon running. ERRα/γ dmKO mice showed no defects in whole-body glucose and energy homeostasis.
conclusionsOur findings define gene expression programs in skeletal muscle that depend on different combinations of ERRs, and establish a central role for ERRs in skeletal muscle oxidative metabolism and exercise capacity. Our data reveal a high degree of functional redundancy among muscle ERR isoforms for the protection of oxidative capacity, and show that ERR isoform-specific phenotypes are driven in part, but not exclusively, by their relative levels in different muscles.
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