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Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases.
- Source :
-
Cell [Cell] 2012 Feb 03; Vol. 148 (3), pp. 421-33. - Publication Year :
- 2012
-
Abstract
- Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca(2+) levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca(2+)-release channel. As a consequence, resveratrol increases NAD(+) and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- 3',5'-Cyclic-AMP Phosphodiesterases chemistry
3',5'-Cyclic-AMP Phosphodiesterases metabolism
AMP-Activated Protein Kinase Kinases
Adipose Tissue, White drug effects
Animals
Cyclic Nucleotide Phosphodiesterases, Type 4 chemistry
Cyclic Nucleotide Phosphodiesterases, Type 4 metabolism
Diet
Glucose Intolerance prevention & control
Guanine Nucleotide Exchange Factors metabolism
Mice
Models, Molecular
Muscle, Skeletal drug effects
NAD metabolism
Obesity prevention & control
Protein Kinases metabolism
Resveratrol
Rolipram administration & dosage
Ryanodine Receptor Calcium Release Channel metabolism
Sirtuin 1 metabolism
3',5'-Cyclic-AMP Phosphodiesterases antagonists & inhibitors
Aging metabolism
Caloric Restriction
Signal Transduction
Stilbenes administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 148
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 22304913
- Full Text :
- https://doi.org/10.1016/j.cell.2012.01.017