학술논문

AMPK and PPARδ Agonists Are Exercise Mimetics
Document Type
Article
Source
Cell. Aug2008, Vol. 134 Issue 3, p405-415. 11p.
Subject
*METABOLIC disorders
*LABORATORY mice
*CELLS
*CYTOLOGY
Language
ISSN
0092-8674
Abstract
Summary: 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 PPARβ/δ agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1α, 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-PPARδ pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise. [Copyright &y& Elsevier]