Evidence map›Paper›PMID 40328250›Full record

ArticleCell reports. Medicine2025

Muscle metabolic resilience and enhanced exercise adaptation by Esr1-induced remodeling of mitochondrial cristae-nucleoid architecture in males.

Zhenqi Zhou, Timothy M Moore, Alexander R Strumwasser, Vicent Ribas, Hirotaka Iwasaki, Noelle Morrow, Alice Ma, Peter H Tran, Jonathan Wanagat, Thomas Q de Aguiar Vallim and 26 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Resistance-based exercise restores muscle health in dialysis patients.Journal of muscle research and cell motility · 2026
    Article
  2. Article
  3. Review
  4. Metabolic Messengers: oestradiol.Nature metabolism · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors.

Zhenqi ZhouDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Timothy M MooreDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Alexander R StrumwasserDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Vicent RibasDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Hirotaka IwasakiDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Noelle MorrowDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Alice MaDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Peter H TranDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jonathan WanagatDivision of Geriatrics, David Geffen School of Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Thomas Q de Aguiar VallimDivision of Cardiology, David Geffen School of Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Bethan CliffordDivision of Cardiology, David Geffen School of Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Zhengyi ZhangDivision of Cardiology, David Geffen School of Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Tamer SallamDivision of Cardiology, David Geffen School of Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Brian W ParksDavid Geffen School of Medicine, Department of Medicine, Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Karen ReueDavid Geffen School of Medicine, Department of Medicine, Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Orian ShirihaiDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Rebeca Acin-PerezDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Marco MorselliDepartment of Molecular, Cell and Developmental Biology and UCLA-DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, CA 900095, USA.
Matteo PellegriniDepartment of Molecular, Cell and Developmental Biology and UCLA-DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, CA 900095, USA.
Sushil K MahataDepartment of Medicine and VA, University of California, San Diego, La Jolla, CA 92037, USA.
Frode NorheimDavid Geffen School of Medicine, Department of Medicine, Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; University Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0316 Oslo, Norway.
Mingqi ZhouDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Marcus M SeldinDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Aldons J LusisDivision of Cardiology, David Geffen School of Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; David Geffen School of Medicine, Department of Medicine, Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cathy C LeeDepartment of Medicine and VA, Greater Los Angeles Healthcare System GRECC, Los Angeles, CA 90073, USA.
Mark O GoodarziDepartment of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.
Joshua R HansenChemical and Biological Signature Sciences Group, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Ben DruckerBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Tyler J SagendorfBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Joshua N AdkinsBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
James A SanfordBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Francesco J DeMayoReproductive Developmental Biology Laboratory, NIEHS, NIH, Research Triangle Park, NC 27709, USA.
Sylvia C HewittReproductive Developmental Biology Laboratory, NIEHS, NIH, Research Triangle Park, NC 27709, USA.
Kenneth S KorachReproductive Developmental Biology Laboratory, NIEHS, NIH, Research Triangle Park, NC 27709, USA.
Andrea L HevenerDavid Geffen School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine and VA, Greater Los Angeles Healthcare System GRECC, Los Angeles, CA 90073, USA; Iris Cantor-UCLA Women's Health Research Center, Los Angeles, CA 90095, USA. Electronic address: ahevener@mednet.ucla.edu.

Funding

ZONA-FREE HAMSTER OVA ASSAY AS AN INDICATOR OF MALE FERTILITYM01RR000425 · NCRR · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI ANDERSON, GAIL V · 1985 to 2011
$74.2M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2M
Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 1985 to 2019
$50.2M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALAN R. SALTIEL · 2003 to 2026
$40.4M
EXPANSION OF NURSA TRANSCRIPTOMINE ANNOTATIONU24DK097748 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI EVANS, RONALD M, MCKENNA, NEIL · 2012 to 2017
$9.2M
Sex Differences in the Metabolic SyndromeU54DK120342 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 2018 to 2022
$7.6M
The impact of estrogen receptor alpha on cardiomyocellular metabolism and healthU54HL170326 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Hooman Allayee · 2023 to 2026
$7.5M
Mapping Genes for Atherosclerosis and Insulin ResistanceR01HL088457 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI ROTTER, JEROME I · 2007 to 2010
$3.0M
Mitochondrial DNA Deletion Mutation Frequency as a Metric of Biologic AgeR01AG069924 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jonathan Wanagat · 2022 to 2026
$2.1M
Insulin Clearance: Candidate and Positional Genetic DeterminantsR01DK079888 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI GOODARZI, MARK · 2008 to 2012
$1.7M
The Role of PPARgamma Expression on Insulin ActionK01DK060484 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HEVENER, ANDREA L · 2002 to 2006
$542k
CSRD VA I01 CX002838NCATS NIH HHS UL1 TR000124NCRR NIH HHS M01 RR000425NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NHLBI NIH HHS R01 HL088457NHLBI NIH HHS U54 HL170326NIA NIH HHS R01 AG069924NIDDK NIH HHS K01 DK060484NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK079888NIDDK NIH HHS U24 DK097748NIDDK NIH HHS U54 DK120342RRD VA I01 RX004521
6 · The paper itself

Abstract

Reduced estrogen action is associated with obesity and insulin resistance. However, the cell and tissue-specific actions of estradiol in maintaining metabolic health remain inadequately understood, especially in men. We observed that skeletal muscle ESR1/Esr1 (encodes estrogen receptor α [ERα]) is positively correlated with insulin sensitivity and metabolic health in humans and mice. Because skeletal muscle is a primary tissue involved in oxidative metabolism and insulin sensitivity, we generated muscle-selective Esr1 loss- and gain-of-expression mouse models. We determined that Esr1 links mitochondrial DNA replication and cristae-nucleoid architecture with metabolic function and insulin action in the skeletal muscle of male mice. Overexpression of human ERα in muscle protected male mice from diet-induced disruption of metabolic health and enhanced mitochondrial adaptation to exercise training intervention. Our findings indicate that muscle expression of Esr1 is critical for the maintenance of mitochondrial function and metabolic health in males and that tissue-selective activation of ERα can be leveraged to combat metabolic-related diseases in both sexes.

Indexed as

Adaptation, PhysiologicalEstrogen Receptor alphaMitochondriaMitochondria, MuscleMuscle, SkeletalPhysical Conditioning, AnimalAnimalsDNA, MitochondrialHumansInsulin ResistanceMaleMiceMice, Inbred C57BLDNA, MitochondrialEstrogen Receptor alphaestrogen actionexercise adaptationinsulin sensitivitymitochondrial cristae architecturemitochondrial functionmtDNA replicationoxidative metabolism

Identifiers

PMID40328250
PMCPMC12147913

What Socratic holds

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Registered trials

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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 Socratic graph.