Evidence map›Paper›PMID 25852572›Full record

ArticleFrontiers in physiology2015

AMP-activated protein kinase controls exercise training- and AICAR-induced increases in SIRT3 and MnSOD.

Josef Brandauer, Marianne A Andersen, Holti Kellezi, Steve Risis, Christian Frøsig, Sara G Vienberg, Jonas T Treebak

Open access · goldAbstract read
In one paragraph

Article in Frontiers in physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 4% of its field
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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. The AMPK Pathway: Molecular Rejuvenation of Metabolism and Mitochondria.Annual review of cell and developmental biology · 2025
    Review
  8. Article
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  11. Review
  12. Complex II Biology in Aging, Health, and Disease.Antioxidants (Basel, Switzerland) · 2023
    Review
  13. Review
  14. Review
  15. Article
  16. Sirtuin-3: A potential target for treating several types of brain injury.Frontiers in cell and developmental biology · 2023
    Review
  17. The Aging Heart: A Molecular and Clinical Challenge.International journal of molecular sciences · 2022
    Review
  18. Review
  19. Article
  20. AMPK and the Adaptation to Exercise.Annual review of physiology · 2022
    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

7 authors at 2 institutions in 2 countries.

Josef BrandauerSection of Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen Copenhagen, Denmark ; Department of Health Sciences, Gettysburg College Gettysburg, PA, USA.
Marianne A AndersenSection of Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen Copenhagen, Denmark.
Holti KelleziSection of Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen Copenhagen, Denmark.
Steve RisisSection of Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen Copenhagen, Denmark.
Christian FrøsigSection of Molecular Physiology, Department of Nutrition, Exercise and Sports, The August Krogh Centre, University of Copenhagen Copenhagen, Denmark.
Sara G VienbergSection of Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen Copenhagen, Denmark.
Jonas T TreebakSection of Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen Copenhagen, Denmark.
University of Copenhagen · DKNovo Nordisk Foundation · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The mitochondrial protein deacetylase sirtuin (SIRT) 3 may mediate exercise training-induced increases in mitochondrial biogenesis and improvements in reactive oxygen species (ROS) handling. We determined the requirement of AMP-activated protein kinase (AMPK) for exercise training-induced increases in skeletal muscle abundance of SIRT3 and other mitochondrial proteins. Exercise training for 6.5 weeks increased SIRT3 (p < 0.01) and superoxide dismutase 2 (MnSOD; p < 0.05) protein abundance in quadriceps muscle of wild-type (WT; n = 13-15), but not AMPK α2 kinase dead (KD; n = 12-13) mice. We also observed a strong trend for increased MnSOD abundance in exercise-trained skeletal muscle of healthy humans (p = 0.051; n = 6). To further elucidate a role for AMPK in mediating these effects, we treated WT (n = 7-8) and AMPK α2 KD (n = 7-9) mice with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR). Four weeks of daily AICAR injections (500 mg/kg) resulted in AMPK-dependent increases in SIRT3 (p < 0.05) and MnSOD (p < 0.01) in WT, but not AMPK α2 KD mice. We also tested the effect of repeated AICAR treatment on mitochondrial protein levels in mice lacking the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PGC-1α KO; n = 9-10). Skeletal muscle SIRT3 and MnSOD protein abundance was reduced in sedentary PGC-1α KO mice (p < 0.01) and AICAR-induced increases in SIRT3 and MnSOD protein abundance was only observed in WT mice (p < 0.05). Finally, the acetylation status of SIRT3 target lysine residues on MnSOD (K122) or oligomycin-sensitivity conferring protein (OSCP; K139) was not altered in either mouse or human skeletal muscle in response to acute exercise. We propose an important role for AMPK in regulating mitochondrial function and ROS handling in skeletal muscle in response to exercise training.

Indexed as

AMPKexercise trainingmitochondrial biogenesisMnSODOSCPROSSIRT3SOD2

Identifiers

PMID25852572
PMCPMC4371692
OpenAlexW2084917808

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.