Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Oct 1;1(4):256-258.
doi: 10.4161/adip.21158.

Metabolic benefits of inhibiting cAMP-PDEs with resveratrol

Jay H Chung  1
Affiliations

Metabolic benefits of inhibiting cAMP-PDEs with resveratrol

Jay H Chung. Adipocyte. .

Abstract

Calorie restriction (CR) extends lifespan in species ranging from yeast to mammals. There is evidence that CR also protects against aging-related diseases in non-human primates. This has led to an intense interest in the development of CR-mimetics to harness the beneficial effects of CR to treat aging-related diseases. One CR-mimetic that has received a great deal of attention is resveratrol. Resveratrol extends the lifespan of obese mice and protects against obesity-related diseases such as type 2 diabetes. The specific mechanism of resveratrol action has been difficult to elucidate because resveratrol has a promiscuous target profile. A recent finding indicates that the metabolic effects of resveratrol may result from competitive inhibition of cAMP-degrading phosphodiesterases (PDEs), which increases cAMP levels. The cAMP-dependent pathways activate AMP-activated protein kinase (AMPK), which is essential for the metabolic effects of resveratrol. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including protection against diet-induced obesity and an increase in mitochondrial function, physical stamina and glucose tolerance in mice. This discovery suggests that PDE inhibitors may be useful for treating metabolic diseases associated with aging.

Keywords: AMP-activated protein kinase; Epac1; Sirt1; aging; cAMP; calorie-restriction; metabolic; phosphodiesterases; resveratrol.

PubMed Disclaimer

Comment on

  • Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 2012;148:421–33. doi: 10.1016/j.cell.2012.01.017.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Fontana L, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Science. 2010;328:321–6. doi: 10.1126/science.1172539. - DOI - PMC - PubMed
    1. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009;325:201–4. doi: 10.1126/science.1173635. - DOI - PMC - PubMed
    1. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004;430:686–9. doi: 10.1038/nature02789. - DOI - PubMed
    1. Gruber J, Tang SY, Halliwell B. Evidence for a trade-off between survival and fitness caused by resveratrol treatment of Caenorhabditis elegans. Ann N Y Acad Sci. 2007;1100:530–42. doi: 10.1196/annals.1395.059. - DOI - PubMed
    1. Viswanathan M, Kim SK, Berdichevsky A, Guarente L. A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell. 2005;9:605–15. doi: 10.1016/j.devcel.2005.09.017. - DOI - PubMed

LinkOut - more resources