ArticleScience translational medicine2016
Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females.
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Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers.
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175citing papers in PubMed
13.4field-weighted citation impact, top 1% of its field
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Who cites it
175 citing papers in PubMed, 251 citations in OpenAlex.
- Leg vascular and skeletal muscle mitochondrial adaptations to aerobic high-intensity exercise training are enhanced in the early postmenopausal phase.The Journal of physiology · 2017Trial
- ERα/SIRT1 signaling mediates the metabolic regulatory benefits of pterostilbene.The Journal of biological chemistry · 2026Article
- Aging is associated with altered estrogen receptor expression and alters redox protein balance in human female skeletal muscle.GeroScience · 2026Article
- Lycopene Increases Skeletal Muscle Mass by Promoting Myoblast Differentiation.Food science & nutrition · 2026Article
- Ginsenoside Rg1 enhances stem cell abundance in aging human skeletal muscle after resistance exercise.Journal of ginseng research · 2026Article
- A Plant-Derived Flavonoid, Isobavachin, Promotes Osteogenesis and Alleviates Glucocorticoid-Induced Osteoporosis via Modulation of the ESR1-PI3K/Akt Signaling Pathway.Molecules (Basel, Switzerland) · 2026Article
- Review
- Cancer IDO1-Mediated Tryptophan-Kynurenine Metabolic Reprogramming to Drive Skeletal Muscle Atrophy and Cachexia Acceleration.Journal of cachexia, sarcopenia and muscle · 2026Article
- TAK1 Regulates Skeletal Muscle Mass, Hypertrophic Signaling, and Metabolic Homeostasis in Male and Female Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Sex Hormones & Exercise in the Musculoskeletal System: From Signaling to Structure and Function.Endocrine reviews · 2026Article
- Joint associations of grip strength, lipid levels, and lipid-related genetic risk with atrial fibrillation.Lipids in health and disease · 2026Article
- Mitochondrial vulnerability underlies myocarditis from COVID-19 mRNA vaccine.Nature communications · 2026Article
- Article
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- Estrogen in skeletal muscle: metabolism, mechanisms, and exercise-induced changes.Journal of endocrinological investigation · 2026Review
- Congenital vs adult-onset estrogen deficiency in female mice: physiological effects and implications for therapy.The Journal of endocrinology · 2026Article
- TAK1 regulates skeletal muscle mass, hypertrophic signaling, and metabolic homeostasis in male and female mice.bioRxiv : the preprint server for biology · 2026Article
- Effects of Voluntary Exercise and Acetic Acid Supplementation on Skeletal Muscle Mitochondrial Function in Ovariectomized Mice.Nutrients · 2026Article
- Modified cardiometabolic index outperforms conventional indices in discriminating relative muscle loss: a cross-sectional analysis of NHANES 2011-2018.European journal of medical research · 2026Article
- Understanding Exercise-induced Protection in Heart Failure with Reduced Ejection Fraction and Heart Failure with Preserved Ejection Fraction: Molecular Mechanisms and New Therapeutic Opportunities.Cardiac failure review · 2026Review
115 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 3 institutions in 2 countries.
Vicent RibasDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Brian G DrewDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Zhenqi ZhouDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Jennifer PhunDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Nareg Y KalajianDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Teo SoleymaniDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Pedram DaraeiDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Kevin WidjajaDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Jonathan WanagatDivision of Geriatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Thomas Q de Aguiar VallimDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Amy H FluittDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Steven BensingerDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Thuc LeDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Ahmanson Translational Imaging Division, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Caius RaduDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Ahmanson Translational Imaging Division, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Julian P WhiteleggePasarow Mass Spectrometry Laboratory and Neuropsychiatric Institute-Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Simon W BeavenHoward Hughes Medical Institute and Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Peter TontonozHoward Hughes Medical Institute and Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Aldons J LusisDivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Brian W ParksDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Laurent VergnesDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Karen ReueDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Harpreet SinghDepartment of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Jean C BopassaDepartment of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Ligia ToroDepartment of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Enrico StefaniDepartment of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Matthew J WattDepartment of Physiology, Monash University, Clayton, Victoria 3800, Australia.
Simon SchenkDepartment of Orthopaedic Surgery, University of California, San Diego, La Jolla, CA 92093, USA.
Thorbjorn AkerstromCentre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen 2200, Denmark.
Meghan KellyCentre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen 2200, Denmark.
Bente K PedersenCentre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen 2200, Denmark.
Sylvia C HewittReceptor Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC 27709, USA.
Kenneth S KorachReceptor Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC 27709, USA.
Andrea L HevenerDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. UCLA Iris Cantor Women's Health Research Center, Los Angeles, CA 90095, USA. ahevener@mednet.ucla.edu.
University of California, Los Angeles · USMonash University · AUUniversity of California, San Diego · US
Funding
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2MSystems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 1985 to 2019
$50.2MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4MChemical Receptor Interactions In Reproduction And Hormonal ToxicityZIAES070065 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KORACH, KENNETH S · 2009 to 2019
$29.6MThe Lipin Protein Family and Triglyceride Metabolism P01HL090553 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2008 to 2018
$23.3MPilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0MEXPANSION OF NURSA TRANSCRIPTOMINE ANNOTATIONU24DK097748 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI EVANS, RONALD M, MCKENNA, NEIL · 2012 to 2017
$9.2MMechanisms controlling skeletal muscle mitochondrial function and metabolic healthR01DK109724 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HEVENER, ANDREA L · 2016 to 2020
$2.4MChloride intracellular channels in cardiac mitochondria and their direct role in cardioprotectionR01HL133050 · NHLBI · OHIO STATE UNIVERSITY · PI SINGH, HARPREET · 2016 to 2020
$2.0MERalpha and the metabolic syndromeR01DK089109 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HEVENER, ANDREA L · 2011 to 2014
$1.4MSystems Genetics Analysis of Gene-by-Environment Interactions in ObesityR00HL123021 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI PARKS, BRIAN WESLEY · 2016 to 2018
$747kNCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCRR NIH HHS S10 RR026744NCRR NIH HHS S10RR026744NHLBI NIH HHS HL28481NHLBI NIH HHS HL30568NHLBI NIH HHS K99 HL123021NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NHLBI NIH HHS P01 HL090553NHLBI NIH HHS R00 HL123021NHLBI NIH HHS R01 HL133050NIDDK NIH HHS DK060484NIDDK NIH HHS DK063491NIDDK NIH HHS DK073227NIDDK NIH HHS DK097748NIDDK NIH HHS K01 DK060484NIDDK NIH HHS K08 DK088998NIDDK NIH HHS P30 DK041301NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK089109NIDDK NIH HHS R01 DK109724NIDDK NIH HHS R21 DK073227NIDDK NIH HHS U24 DK097748
Abstract
Impaired estrogen receptor α (ERα) action promotes obesity and metabolic dysfunction in humans and mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal and oxidative metabolism, we established that reduced ERα expression in muscle is associated with glucose intolerance and adiposity in women and female mice. To test this relationship, we generated muscle-specific ERα knockout (MERKO) mice. Impaired glucose homeostasis and increased adiposity were paralleled by diminished muscle oxidative metabolism and bioactive lipid accumulation in MERKO mice. Aberrant mitochondrial morphology, overproduction of reactive oxygen species, and impairment in basal and stress-induced mitochondrial fission dynamics, driven by imbalanced protein kinase A-regulator of calcineurin 1-calcineurin signaling through dynamin-related protein 1, tracked with reduced oxidative metabolism in MERKO muscle. Although muscle mitochondrial DNA (mtDNA) abundance was similar between the genotypes, ERα deficiency diminished mtDNA turnover by a balanced reduction in mtDNA replication and degradation. Our findings indicate the retention of dysfunctional mitochondria in MERKO muscle and implicate ERα in the preservation of mitochondrial health and insulin sensitivity as a defense against metabolic disease in women.
Indexed as
AnimalsAutophagyCalcium-Binding ProteinsDNA, MitochondrialDNA ReplicationDynaminsEstrogen Receptor alphaFemaleGene DeletionGlucoseHomeostasisHumansInsulinIntracellular Signaling Peptides and ProteinsLipid MetabolismMiceCalcium-Binding ProteinsDNA, MitochondrialDnm1l protein, mouseDSCR1 protein, mouseDynaminsEstrogen Receptor alphaGlucoseInsulinIntracellular Signaling Peptides and ProteinsMuscle ProteinsReactive Oxygen Species
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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 OpenQuestion graph.