ArticleFASEB bioAdvances2022
Estrogen-related receptor alpha is an AMPK-regulated factor that promotes ischemic muscle revascularization and recovery in diet-induced obese mice.
Article in FASEB bioAdvances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Retrograde mitochondrial transport is required for mitochondrial biogenesis in zebrafish neurons.Nature communications · 2026Article
- Hepatocyte estrogen-related receptor α modulates a gluconeogenic-epigenetic crosstalk counteracting MASLD/MASH progression.Experimental & molecular medicine · 2026Article
- The nonsteroidal MR antagonist finerenone reverses Western diet-induced kidney disease by regulating mitochondrial and lipid metabolism and inflammation.American journal of physiology. Renal physiology · 2025Article
- 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
- Retrograde mitochondrial transport regulates mitochondrial biogenesis in zebrafish neurons.bioRxiv : the preprint server for biology · 2025Article
- The AMPK Pathway: Molecular Rejuvenation of Metabolism and Mitochondria.Annual review of cell and developmental biology · 2025Review
- Nuclear receptors in metabolic, inflammatory, and oncologic diseases: mechanisms, therapeutic advances, and future directions.European journal of medical research · 2025Review
- The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy through TFEB.Molecular pharmacology · 2024Article
- Review
- Sexual Dimorphism in Cardiometabolic Diseases: The Role of AMPK.International journal of molecular sciences · 2023Review
- Estrogen-related Receptor Signaling in Skeletal Muscle Fitness.International journal of sports medicine · 2023Article
- The Role of the Estrogen-Related Receptor Alpha (ERRa) in Hypoxia and Its Implications for Cancer Metabolism.International journal of molecular sciences · 2023Review
- Innately expressed estrogen-related receptors in the skeletal muscle are indispensable for exercise fitness.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Roles of Estrogen, Estrogen Receptors, and Estrogen-Related Receptors in Skeletal Muscle: Regulation of Mitochondrial Function.International journal of molecular sciences · 2023Review
- Exercise and Ischemia-Activated Pathways in Limb Muscle Angiogenesis and Vascular Regeneration.Methodist DeBakey cardiovascular journal · 2023Review
- Estrogen-related receptor alpha is an AMPK-regulated factor that promotes ischemic muscle revascularization and recovery in diet-induced obese mice.FASEB bioAdvances · 2022Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Obesity and type II diabetes are leading causes of peripheral arterial disease (PAD), which is characterized by vascular insufficiency and ischemic damage in the limb skeletal muscle. Glycemic control is not sufficient to prevent progression of PAD, and molecular targets that can promote muscle neo-angiogenesis in obesity and diabetes remain poorly defined. Here, we have investigated whether nuclear receptor estrogen-related receptor alpha (ERRα) can promote ischemic revascularization in the skeletal muscles of diet-induced obese (DIO) mice. Using muscle-specific ERRα transgenic mice, we found that ERRα overexpression promotes revascularization, marked by increased capillary staining and muscle perfusion in DIO mice after hindlimb ischemic injury. Furthermore, ERRα facilitates repair and restoration of skeletal muscle myofiber size after limb ischemia in DIO mice. The ameliorative effects of ERRα overexpression did not involve the prevention of weight gain, hyperglycemia or glucose/insulin intolerance, suggesting a direct role for ERRα in promoting angiogenesis. Interestingly, levels of endogenous ERRα protein are suppressed in the skeletal muscles of DIO mice compared to lean controls, coinciding with the suppression of angiogenic gene expression, and reduced AMPK signaling in the DIO skeletal muscles. Upon further investigating the link between AMPK and ERRα, we found that AMPK activation increases the expression and recruitment of ERRα protein to specific angiogenic gene promoters in muscle cells. Further, the induction of angiogenic factors by AMPK activators in muscle cells is blocked by repressing ERRα. In summary, our results identify an AMPK/ERRα-dependent angiogenic gene program in the skeletal muscle, which is repressed by DIO, and demonstrate that forced ERRα activation can promote ischemic revascularization and muscle recovery in obesity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.