Abstract

Resveratrol is a polyphenol found in plants and plant-based foods. Resveratrol protects against obesity and obesity-related diseases such as type 2 diabetes. The mechanism by which resveratrol confers these benefits is not known. We discovered that the metabolic benefits of resveratrol are mediated by inhibiting phosphodiesterase 4 in skeletal muscle. Resveratrol has also been reported to activate Sirt1. In mammals, the Sirtuins are composed of seven Sir2 orthologues (Sirt1-7) with a conserved deacetylase core that utilizes NAD+ as a cofactor. Sirtuins play an important role in energy metabolism and regulating Sirtuin activity may be useful for controlling fat accumulation. We found that resveratrol increases Sirt1 activity by increasing NAD+ in an AMPK-dependent manner.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006118-02
Application #
8558057
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2012
Total Cost
$1,108,695
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Kang, Hyeog; Oka, Shinichi; Lee, Duck-Yeon et al. (2017) Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins. Nat Commun 8:15560
Park, Sung-Jun; Ahmad, Faiyaz; Um, Jee-Hyun et al. (2017) Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK. EBioMedicine 18:128-138
Bitterman, Jacob L; Chung, Jay H (2015) Metabolic effects of resveratrol: addressing the controversies. Cell Mol Life Sci 72:1473-88
Mishra, Amarjit; Brown, Alexandra L; Yao, Xianglan et al. (2015) Dendritic cells induce Th2-mediated airway inflammatory responses to house dust mite via DNA-dependent protein kinase. Nat Commun 6:6224
Park, Jun Hong; Kang, Hong-Jun; Lee, Yun Kyung et al. (2015) Inactivation of EWS reduces PGC-1? protein stability and mitochondrial homeostasis. Proc Natl Acad Sci U S A 112:6074-9
Maurice, Donald H; Ke, Hengming; Ahmad, Faiyaz et al. (2014) Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov 13:290-314
Um, Jee-Hyun; Brown, Alexandra L; Singh, Samarendra K et al. (2013) Metabolic sensor AMPK directly phosphorylates RAG1 protein and regulates V(D)J recombination. Proc Natl Acad Sci U S A 110:9873-8
Chung, Jay H (2012) Metabolic benefits of inhibiting cAMP-PDEs with resveratrol. Adipocyte 1:256-258
Chung, Jay H (2012) Using PDE inhibitors to harness the benefits of calorie restriction: lessons from resveratrol. Aging (Albany NY) 4:144-5
Park, Sung-Jun; Ahmad, Faiyaz; Philp, Andrew et al. (2012) Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148:421-33

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