AMPK and PPARdelta agonists are exercise mimetics
- PMID: 18674809
- PMCID: PMC2706130
- DOI: 10.1016/j.cell.2008.06.051
AMPK and PPARdelta agonists are exercise mimetics
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.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2706130/bin/nihms-65540-f0001.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2706130/bin/nihms-65540-f0002.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2706130/bin/nihms-65540-f0003.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2706130/bin/nihms-65540-f0004.gif)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2706130/bin/nihms-65540-f0005.gif)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2706130/bin/nihms-65540-f0006.gif)
Comment in
- Cell. 2008 Oct 3;135(1):189
Similar articles
-
Combined pharmacological activation of AMPK and PPARδ potentiates the effects of exercise in trained mice.Physiol Rep. 2016 Mar;4(5):e12625. doi: 10.14814/phy2.12625. Physiol Rep. 2016. PMID: 26997622 Free PMC article.
-
Metabolic modulators of the exercise response: doping control analysis of an agonist of the peroxisome proliferator-activated receptor δ (GW501516) and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR).J Physiol Pharmacol. 2014 Aug;65(4):469-76. J Physiol Pharmacol. 2014. PMID: 25179079 Review.
-
The exercise pill--too good to be true?N Engl J Med. 2008 Oct 23;359(17):1842-4. doi: 10.1056/NEJMcibr0806723. N Engl J Med. 2008. PMID: 18946072 No abstract available.
-
Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E310-7. doi: 10.1152/ajpendo.00074.2004. Epub 2004 Apr 6. Am J Physiol Endocrinol Metab. 2004. PMID: 15068958
-
AMP-activated protein kinase: possible target for treatment of type 2 diabetes.Diabetes Technol Ther. 2000 Autumn;2(3):441-8. doi: 10.1089/15209150050194305. Diabetes Technol Ther. 2000. PMID: 11467346 Review.
Cited by
-
Mitochondrial quality control in human health and disease.Mil Med Res. 2024 May 29;11(1):32. doi: 10.1186/s40779-024-00536-5. Mil Med Res. 2024. PMID: 38812059 Free PMC article. Review.
-
Eicosapentaenoic acid increases proportion of type 1 muscle fibers through PPARδ and AMPK pathways in rats.iScience. 2024 Apr 26;27(6):109816. doi: 10.1016/j.isci.2024.109816. eCollection 2024 Jun 21. iScience. 2024. PMID: 38779480 Free PMC article.
-
AMPK as a mediator of tissue preservation: time for a shift in dogma?Nat Rev Endocrinol. 2024 May 17. doi: 10.1038/s41574-024-00992-y. Online ahead of print. Nat Rev Endocrinol. 2024. PMID: 38760482 Review.
-
Complementary information concerning the suspected interindividual transmission of GW1516, a substance prohibited in sport, through intimate contact: a case report.Forensic Toxicol. 2024 May 5. doi: 10.1007/s11419-024-00689-x. Online ahead of print. Forensic Toxicol. 2024. PMID: 38704758
-
Mitochondrial Transplantation's Role in Rodent Skeletal Muscle Bioenergetics: Recharging the Engine of Aging.Biomolecules. 2024 Apr 18;14(4):493. doi: 10.3390/biom14040493. Biomolecules. 2024. PMID: 38672509 Free PMC article.
References
-
- Andersson U, Filipsson K, Abbott CR, Woods A, Smith K, Bloom SR, Carling D, Small CJ. AMP-activated protein kinase plays a role in the control of food intake. J. Biol. Chem. 2004;279:12005–8. - PubMed
-
- Booth FW, Thomason DB. Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models. Physiol. Rev. 1991;71:541–85. - PubMed
-
- Bassel-Duby R, Olson EN. Signaling pathways in skeletal muscle remodeling. Annu. Rev. Biochem. 2006;75:19–37. - PubMed
-
- Chen ZP, Stephens TJ, Murthy S, Canny BJ, Hargreaves M, Witters LA, Kemp BE, McConell GK. Effect of exercise intensity on skeletal muscle AMPK signaling in humans. Diabetes. 2003;52:2205–12. - PubMed
Publication types
MeSH terms
Substances
Associated data
- Actions
Grants and funding
- F32 AR053803-03/AR/NIAMS NIH HHS/United States
- R01 HD027183/HD/NICHD NIH HHS/United States
- R37 DK057978-30/DK/NIDDK NIH HHS/United States
- R01 HD027183-17/HD/NICHD NIH HHS/United States
- R37 DK057978/DK/NIDDK NIH HHS/United States
- F32 AR053803-02/AR/NIAMS NIH HHS/United States
- DK057978/DK/NIDDK NIH HHS/United States
- HD027183/HD/NICHD NIH HHS/United States
- F32 AR053803-01/AR/NIAMS NIH HHS/United States
- F32 AR053803/AR/NIAMS NIH HHS/United States
- HHMI/Howard Hughes Medical Institute/United States
- R01 DK057978/DK/NIDDK NIH HHS/United States
- P30 CA014195/CA/NCI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases