Document Detail

AMPK and PPARdelta agonists are exercise mimetics.
MedLine Citation:
PMID:  18674809     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-07-31
Journal Detail:
Title:  Cell     Volume:  134     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-11     Completed Date:  2008-09-02     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  405-15     Citation Subset:  IM    
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MeSH Terms
AMP-Activated Protein Kinases
Administration, Oral
Aminoimidazole Carboxamide / administration & dosage,  analogs & derivatives*,  pharmacology
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
AR053803-03/AR/NIAMS NIH HHS; DK057978/DK/NIDDK NIH HHS; F32 AR053803/AR/NIAMS 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
Reg. No./Substance:
0/GW 501516; 0/Multienzyme Complexes; 0/PPAR delta; 0/Ribonucleotides; 0/Thiazoles; 360-97-4/Aminoimidazole Carboxamide; EC Protein Kinases; EC Kinases; F0X88YW0YK/AICA ribonucleotide

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