| AMPK and PPARdelta agonists are exercise mimetics. | |
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MedLine Citation:
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PMID: 18674809 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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:
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Vihang A Narkar; Michael Downes; Ruth T Yu; Emi Embler; Yong-Xu Wang; Ester Banayo; Maria M Mihaylova; Michael C Nelson; Yuhua Zou; Henry Juguilon; Heonjoong Kang; Reuben J Shaw; Ronald M Evans |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-07-31 |
Journal Detail:
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Title: Cell Volume: 134 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2008 Aug |
Date Detail:
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Created Date: 2008-08-11 Completed Date: 2008-09-02 Revised Date: 2013-05-08 |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 405-15 Citation Subset: IM |
Affiliation:
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Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE11805 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases Administration, Oral Aminoimidazole Carboxamide / administration & dosage, analogs & derivatives*, pharmacology Animals Biomimetics Male Mice Mice, Inbred C57BL Multienzyme Complexes / metabolism* Muscle, Skeletal / metabolism* PPAR delta / agonists* Physical Conditioning, Animal Physical Endurance / drug effects* Protein-Serine-Threonine Kinases / metabolism* Ribonucleotides / administration & dosage, pharmacology* Thiazoles / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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AR053803-03/AR/NIAMS NIH HHS; DK057978/DK/NIDDK NIH HHS; F32 AR053803-01/AR/NIAMS NIH HHS; F32 AR053803-02/AR/NIAMS NIH HHS; F32 AR053803-03/AR/NIAMS NIH HHS; HD027183/HD/NICHD NIH HHS; P30 CA014195/CA/NCI NIH HHS; R01 HD027183/HD/NICHD NIH HHS; R01 HD027183-17/HD/NICHD NIH HHS; R37 DK057978/DK/NIDDK NIH HHS; R37 DK057978-30/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/GW 501516; 0/Multienzyme Complexes; 0/PPAR delta; 0/Ribonucleotides; 0/Thiazoles; 360-97-4/Aminoimidazole Carboxamide; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases; F0X88YW0YK/AICA ribonucleotide |
| Comments/Corrections | |
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