Cited by 1,222Peroxisome Proliferator-Activated ReceptorsMetabolism, Diabetes, and CancerAdipose Tissue and Metabolism

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AMPK and PPARδ Agonists Are Exercise Mimetics

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Narkar, Vihang A., Downes, Michael, Yu, Ruth T., Embler, Emi, Wang, Yong-Xu, Banayo, Ester, Mihaylova, Maria M., Nelson, Michael C., Zou, Yuhua, Juguilon, Henry, Kang, Heonjoong, Shaw, Reuben J., Evans, Ronald M.·2008·Cell

DOI 10.1016/j.cell.2008.06.051PMC PMC2706130

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Abstract

The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metabolic targets remain elusive. We therefore tested the effect of pathway-specific drugs on endurance capacities of mice in a treadmill running test. We found that PPARbeta/delta agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1alpha, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. These results demonstrate that AMPK-PPARdelta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise.

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Authors: Narkar, V. A., Downes, M., Yu, R. T., Embler, E., Wang, Y.-X., Banayo, E., Mihaylova, M. M., Nelson, M. C., Zou, Y., Juguilon, H., Kang, H., Shaw, R. J., & Evans, R. M.
Affiliations: Salk Institute for Biological Studies (US)
University of Massachusetts Chan Medical School (US)
Howard Hughes Medical Institute (US)
Seoul National University (KR)
Corresponding author: Evans, Ronald M.
ORCID: Narkar, Vihang A.
Downes, Michael
Yu, Ruth T.
Mihaylova, Maria M.
Nelson, Michael C.
Kang, Heonjoong
Shaw, Reuben J.
Evans, Ronald M.
Venue: Cell
Publisher: Elsevier BV
Published: 2008-08
Volume: 134
Issue: 3
Pages: 405-415
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2008.06.051
PMC: PMC2706130
OpenAlex: W2061075485
Cited by: 1,222
References: 54
Citations by year: 2026: 45 · 2025: 30 · 2024: 43 · 2023: 46 · 2022: 35 · 2021: 58 · 2020: 68 · 2019: 56 · 2018: 76 · 2017: 74 · 2016: 58 · 2015: 89 · 2014: 95 · 2013: 97 · 2012: 80
FWCI: 37.75
Type: journal article
Language: en
Update notices: erratum (2008-10-03)
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1847 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
National Cancer Institute (P30CA014195)
National Institute of Diabetes and Digestive and Kidney Diseases (R37DK057978, DK057978, R01DK057978)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (F32AR053803)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD027183, HD027183)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: AMPK agonists, PPARδ agonist, exercise mimetics, AICAR, running endurance, PGC-1α, PPARδ, metabolic adaptation, sedentary mice, metabolic disorders, treadmill running
MeSH terms: Administration, Oral, Aminoimidazole Carboxamide, Animals, Male, Mice, Inbred C57BL, Multienzyme Complexes, Physical Conditioning, Animal, Physical Endurance, Ribonucleotides, Thiazoles, Protein Serine-Threonine Kinases, Muscle, Skeletal, Biomimetics, PPAR delta, Mice, AMP-Activated Protein Kinases

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AMPK and PPARδ Agonists Are Exercise Mimetics

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