The Impact of Skeletal Muscle ERα on Mitochondrial Function and Metabolic Health
Open accessAbstract
The incidence of chronic disease is elevated in women after menopause. Increased expression of ESR1 (the gene that encodes the estrogen receptor alpha, ERα) in muscle is highly associated with metabolic health and insulin sensitivity. Moreover, reduced muscle expression levels of ESR1 are observed in women, men, and animals presenting clinical features of the metabolic syndrome (MetSyn). Considering that metabolic dysfunction elevates chronic disease risk, including type 2 diabetes, heart disease, and certain cancers, treatment strategies to combat metabolic dysfunction and associated pathologies are desperately needed. This review will provide published work supporting a critical and protective role for skeletal muscle ERα in the regulation of mitochondrial function, metabolic homeostasis, and insulin action. We will provide evidence that muscle-selective targeting of ERα may be effective for the preservation of mitochondrial and metabolic health. Collectively published findings support a compelling role for ERα in the control of muscle metabolism via its regulation of mitochondrial function and quality control. Studies identifying ERα-regulated pathways essential for disease prevention will lay the important foundation for the design of novel therapeutics to improve metabolic health of women while limiting secondary complications that have historically plagued traditional hormone replacement interventions.
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Estrogen actions in skeletal muscle, liver, adipose tissue, and immune cells are involved in insulin sensitivity and prevention of lipid accumulation and inflammation.
“Estrogen actions in skeletal muscle, liver, adipose tissue, and immune cells are involved in insulin sensitivity as well as prevention of lipid accumulation and inflammation [20,21,67,68].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [21]
The sections “Estrogen Action, Metabolic Function, and Insulin Sensitivity” and “ERα and Skeletal Muscle Fatty Acid Metabolism” link estrogen or ERα to insulin sensitivity, fat mass, inflammatory markers, and lipid accumulation in muscle (page numbers unavailable in our copy). They do not establish the claimed protective actions in all four listed tissues and cell types: the paper says the specific role of adipose ERα remains unresolved, and the retrieved passages do not show a corresponding role for immune cells. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSignificant sex differences and sex hormone influences on carbohydrate and lipid metabolism are apparent.
“Significant sex differences and sex hormone influences on carbohydrate and lipid metabolism are apparent”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [21]
Important sex differences exist in mitochondrial function, substrate utilization, insulin sensitivity, immune responses, muscle morphology and body composition, iron metabolism, thermoregulation, hydration, appetite control, and energy availability and endocrine function.
“important sex differences exist in mitochondrial function [14–16], substrate utilization, and insulin sensitivity [17–24], immune responses [25–28], muscle morphology and body composition [29–32], iron metabolism [33–40], thermoregulation [41–44], hydration [45,46]{Sims, 2008 #55, [47–53], appetite control [54–59], and energy availability and endocrine function [60–65].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [21]
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Cited by
Sorted by citations
International society of sports nutrition position stand: nutritional concerns of the female athlete
Sims, S. T., Kerksick, C. M., Smith-Ryan, A. E., Janse de Jonge, X. A. K., Hirsch, K. R., Arent, S. M., Hewlings, S. J., Kleiner, S. M., Bustillo, E., Tartar, J. L., et al. (2023) · Journal of the International Society of Sports Nutrition · doi:10.1080/15502783.2023.2204066 · Cited by 91 · see citing works
“intake, energy expenditure, and white adipose tissue distribution [22,66,67].”
Background
- Authors
- Hevener, A. L., Ribas, V., Moore, T. M., & Zhou, Z.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Hevener, Andrea L
- Ribas, Vicent
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2020-02-01
- Volume
- 161
- Issue
- 2
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC7017798
- OpenAlex
- W3006130017
- Cited by
- 54
- References
- 170
- Citations by year
- 2026: 12 · 2025: 5 · 2024: 8 · 2023: 10 · 2022: 9 · 2021: 6 · 2020: 4
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- National Institutes of Health (DK89109, DK063491)
- NIH Nuclear Receptor Signaling Atlas (U24DK097748)
- UCLA Department of Medicine
- Iris Cantor-UCLA Women’s Health Research Foundation
- UCLA Jonsson Comprehensive Cancer Center
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- estrogen receptor alpha, skeletal muscle, mitochondrial function, mitochondrial quality control, metabolic health, insulin sensitivity, metabolic syndrome, menopause, type 2 diabetes, hormone replacement therapy, women's health
- MeSH terms
- Animals, Energy Metabolism, Estradiol, Fatty Acids, Gene Expression Regulation, Humans, Insulin Resistance, Mitochondria, Muscle, Skeletal, Estrogen Receptor alpha
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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