The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
AMPK and PPARδ Agonists Are Exercise Mimetics
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“AICAR also rescued mitochondrial function in mice deficient in cytochrome c oxidase and augmented exercise endurance in healthy animals in a PGC1α-dependent manner, even if they were untrained (255, 256).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [256]
In the citing paper
“Recently, Narkar et al., showed that treatment of mice with a combination of AICAR and GW1516, an agonist of muscle-specific transcriptional regulator PPARδ, synergistically increased oxidative myofibers and running endurance 161.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [161]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Calcium's Role in Mechanotransduction during Muscle Development
Damm, T. B., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,552
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491
AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
Hardie, D. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2249 · Cited by 2,261
Adaptations of skeletal muscle to endurance exercise and their metabolic consequences
Holloszy, J. O., & Coyle, E. F. (1984) · Journal of Applied Physiology · doi:10.1152/jappl.1984.56.4.831 · Cited by 1,985
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950
Self-citationAMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
Minokoshi, Y., Alquier, T., Furukawa, N., Kim, Y.-B., Lee, A., Xue, B., Mu, J., Foufelle, F., Ferré, P., Birnbaum, M. J., et al. (2004) · Nature · doi:10.1038/nature02440 · Cited by 1,637
Peroxisome-Proliferator-Activated Receptor δ Activates Fat Metabolism to Prevent Obesity
Wang, Y.-X., Lee, C.-H., Tiep, S., Yu, R. T., Ham, J., Kang, H., & Evans, R. M. (2003) · Cell · doi:10.1016/s0092-8674(03)00269-1 · Cited by 1,296
Self-citationRegulation of Muscle Fiber Type and Running Endurance by PPARδ
Wang, Y.-X., Zhang, C.-L., Yu, R. T., Cho, H. K., Nelson, M. C., Bayuga-Ocampo, C. R., Ham, J., Kang, H., & Evans, R. M. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020294 · Cited by 1,089
Self-citationRando, T. A., & Blau, H. M. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.125.6.1275 · Cited by 944
The Effect of Endurance Training on Parameters of Aerobic Fitness
Jones, A. M., & Carter, H. (2000) · Sports Medicine · doi:10.2165/00007256-200029060-00001 · Cited by 935
Mu, J., Brozinick, J. T., Valladares, O., Bucan, M., & Birnbaum, M. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00251-9 · Cited by 924
Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake
Kubota, N., Yano, W., Kubota, T., Yamauchi, T., Itoh, S., Kumagai, H., Kozono, H., Takamoto, I., Okamoto, S., Shiuchi, T., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.06.003 · Cited by 844
Signaling Pathways in Skeletal Muscle Remodeling
Bassel‐Duby, R., & Olson, E. N. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142622 · Cited by 823
AMP-activated Protein Kinase Plays a Role in the Control of Food Intake
Andersson-Hall, U. K., Filipsson, K., Abbott, C. R., Woods, A., Smith, K. L., Bloom, S. R., Carling, D., & Small, C. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c300557200 · Cited by 777
Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models
Booth, F. W., & Thomason, D. B. (1991) · Physiological Reviews · doi:10.1152/physrev.1991.71.2.541 · Cited by 703
Peroxisome proliferator‐activated receptor δ controls muscle development and oxydative capability
Luquet, S., Lopez‐Soriano, J., Holst, D., Fredenrich, A., Melki, J., Rassoulzadegan, M., & Grimaldi, P. A. (2003) · The FASEB Journal · doi:10.1096/fj.03-0269fje · Cited by 509
Molecular basis of skeletal muscle plasticity-from gene to form and function
Flück, M., & Hoppeler, H. H. (2003) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/s10254-002-0004-7 · Cited by 493
Koves, T. R., Li, P., An, J., Akimoto, T., Slentz, D., Ilkayeva, O., Dohm, G. L., Yan, Z., Newgard, C. B., & Muoio, D. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507621200 · Cited by 464
Cheng, L., Ding, G., Qin, Q., Huang, Y., Lewis, W., He, N., Evans, R. M., Schneider, M. D., Brako, F. A., Xiao, Y., et al. (2004) · Nature Medicine · doi:10.1038/nm1116 · Cited by 453
Self-citationAnalysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise
Mahoney, D. J., Parise, G., Melov, S., Safdar, A., & Tarnopolsky, M. A. (2005) · The FASEB Journal · doi:10.1096/fj.04-3149fje · Cited by 429
Schuler, M. J., Ali, F., Chambon, C., Duteil, D., Bornert, J., Tardivel, A., Desvergne, B., Wahli, W., Chambon, P., & METZGER, D. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.10.003 · Cited by 378
The role of AMP‐activated protein kinase in mitochondrial biogenesis
Reznick, R. M., & Shulman, G. I. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.109512 · Cited by 375
Dressel, U., Allen, T. L., Pippal, J. B., Rohde, P. R., Lau, P., & Muscat, G. E. O. (2003) · Molecular Endocrinology · doi:10.1210/me.2003-0151 · Cited by 370
Effect of Exercise Intensity on Skeletal Muscle AMPK Signaling in Humans
Chen, Z.-P., Stephens, T. J., Murthy, S., Canny, B. J., Hargreaves, M., Witters, L. A., Kemp, B. E., & McConell, G. K. (2003) · Diabetes · doi:10.2337/diabetes.52.9.2205 · Cited by 369
Skeletal Muscle Adaptation to Exercise Training
Röckl, K. S. C., Hirshman, M. F., Brandauer, J., FUJII, N. L., Witters, L. A., & Goodyear, L. J. (2007) · Diabetes · doi:10.2337/db07-0255 · Cited by 316
PPARδ is a very low-density lipoprotein sensor in macrophages
Chawla, A., Lee, C.-H., Barak, Y., He, W., Rosenfeld, J., Liao, D., Han, J., Kang, H., & Evans, R. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337331100 · Cited by 305
Self-citationPhysiology of Professional Road Cycling
Lucı́a, A., Hoyos, J., & Chicharro, J. L. (2001) · Sports Medicine · doi:10.2165/00007256-200131050-00004 · Cited by 296
Hong, Y. H., Varanasi, U. S., Yang, W., & Leff, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304112200 · Cited by 220
Goodyear, L. J., Chang, P.-Y., Sherwood, D. J., Dufresne, S. D., & Moller, D. E. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.271.2.e403 · Cited by 211
Sprecher, D. L., Massien, C., Pearce, G., Billin, A. N., Perlstein, I., Willson, T. M., Hassall, D. G., Ancellin, N., Patterson, S. D., Lobe, D. C., et al. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000252790.70572.0c · Cited by 207
Garnier, A., Fortin, D., Zoll, J., N’guessan, B. B., Mettauer, B., Lampert, E., Veksler, V., & Ventura‐Clapier, R. (2005) · The FASEB Journal · doi:10.1096/fj.04-2173com · Cited by 193
Short, K. R., Vittone, J. L., Bigelow, M. L., Proctor, D. N., Coenen-Schimke, J. M., Rys, P. N., & Nair, K. S. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00129.2005 · Cited by 187
Krämer, D. K., Al-Khalili, L., Guigas, B., Leng, Y., Garcia-Roves, P. M., & Krook, A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702329200 · Cited by 180
AMP-activated protein kinase regulates gene expression by direct phosphorylation of nuclear proteins
Leff, T. (2003) · Biochemical Society Transactions · doi:10.1042/bst0310224 · Cited by 161
Frøsig, C., Jørgensen, S. B., Hardie, D. G., Richter, E. A., & Wojtaszewski, J. F. P. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00317.2003 · Cited by 161
Exercise Increases Nuclear AMPK α2 in Human Skeletal Muscle
McGee, S. L., Howlett, K. F., Starkie, R. L., Cameron-Smith, D., Kemp, B. E., & Hargreaves, M. (2003) · Diabetes · doi:10.2337/diabetes.52.4.926 · Cited by 160
Timmons, J. A., Larsson, O. S., Jansson, E., Fischer, H., Gustafsson, T. P., Greenhaff, P. L., Ridden, J., Rachman, J., Peyrard‐Janvid, M., Wahlestedt, C., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-1980com · Cited by 159
Thomson, D. M., Porter, B. B., Tall, J. H., Kim, H.-J., Barrow, J. R., & Winder, W. W. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00366.2006 · Cited by 146
Durante, P. E., Mustard, K. J., Park, S.-H., Winder, W. W., & Hardie, D. G. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00404.2001 · Cited by 137
Krämer, D. K., Al-Khalili, L., Perrini, S., Skogsberg, J., Wretenberg, P., Kannisto, K., Wallberg-Henriksson, H., Ehrenborg, E., Zierath, J. R., & Krook, A. (2005) · Diabetes · doi:10.2337/diabetes.54.4.1157 · Cited by 132
Schmitt, B., Flück, M., Décombaz, J., Kreis, R., Boesch, C., Wittwer, M., Graber, F., Vogt, M., HOWALD, H., & Hoppeler, H. H. (2003) · Physiological Genomics · doi:10.1152/physiolgenomics.00089.2003 · Cited by 103
Bronner, M., Hertz, R., & Bar‐Tana, J. (2004) · Biochemical Journal · doi:10.1042/bj20040955 · Cited by 95
Hsiao, A., Worrall, D. S., Olefsky, J. M., & Subramaniam, S. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth371 · Cited by 89
Man, M., Barish, G. D., Schmuth, M., Crumrine, D. A., Barak, Y., Chang, S., Jiang, Y. J., Evans, R. M., Elias, P. M., & Feingold, K. R. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701026 · Cited by 86
Self-citationSkeletal muscle wasting and contractile performance in septic rats
Minnaard, R., Drost, M. R., Wagenmakers, A. J. M., van Kranenburg, G., Kuipers, H., & Hesselink, M. K. C. (2004) · Muscle & Nerve · doi:10.1002/mus.20268 · Cited by 76
Siu, P. M., Donley, D., Bryner, R. W., & Alway, S. E. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00534.2004 · Cited by 65
Software and methods for oligonucleotide and cDNA array data analysis
Zapala, M. A., Lockhart, D. J., Pankratz, D. G., Garcia, A. J., Barlow, C., & Lockhart, D. J. (2002) · Genome biology · doi:10.1186/gb-2002-3-6-software0001 · Cited by 45
Regional differences in adipose tissue metabolism between sedentary and endurance-trained women.
Mauriège, P., Prud’homme, D., Marcotte, M., Yoshioka, M., Tremblay, A., & Després, J. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.3.e497 · Cited by 45
Yoshioka, M., Tanaka, H., Shono, N., Snyder, E. E., Shindo, M., & St‐Amand, J. (2003) · The FASEB Journal · doi:10.1096/fj.02-1200com · Cited by 38
PPARδ activator GW-501516 has no acute effect on glucose transport in skeletal muscle
Terada, S., Wicke, S., Holloszy, J. O., & Han, D. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00430.2005 · Cited by 32
Mahoney, D. J., & Tarnopolsky, M. A. (2005) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2005.08.018 · Cited by 30
Inactivation of myosin heavy chain genes in the mouse: Diverse and unexpected phenotypes
Allen, D. L., Harrison, B. C., & Leinwand, L. A. (2000) · Microscopy Research and Technique · doi:10.1002/1097-0029(20000915)50:6 · Cited by 26
Flagged first, then by citations
Cited by
Sorted by citations
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
AMPK: guardian of metabolism and mitochondrial homeostasis
Herzig, S., & Shaw, R. J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.95 · Cited by 4,192
Self-citationFiber Types in Mammalian Skeletal Muscles
Schiaffino, S., & Reggiani, C. (2011) · Physiological Reviews · doi:10.1152/physrev.00031.2010 · Cited by 3,022
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923
Self-citationFuller, N. R., Colagiuri, S., SCHOFIELD, D. J., Olson, A. D., Shrestha, R. N., Holzapfel, C., Wolfenstetter, S. B., Holle, R., Ahern, A. L., Hauner, H., et al. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.139 · Cited by 2,127
Metadata
- 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
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 134
- Issue
- 3
- Pages
- 405-415
- ISSN
- 0092-8674 (ISSN-L)
- 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
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 ›
Are you an author, or do you see a problem with this page? Request a review
