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Effects of SRT1720 (SRT) and Resveratrol (RSV) on AMP‐activated protein kinase (AMPK) and PKA‐signaling in Adipocytes: Roles for Phosphodiesterase (PDE) (3 and 4)
Author(s) -
KHAN FAIYAZ AHMAD,
Park SungJun,
Chung Jay H,
Manganiello Vincent c
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.604.3
Subject(s) - ampk , protein kinase a , phosphorylation , chemistry , rolipram , phosphodiesterase , microbiology and biotechnology , amp activated protein kinase , phosphodiesterase 3 , signal transduction , endocrinology , medicine , biochemistry , biology , enzyme
SIRT1 activators, SRT and RSV mimic effects of caloric restriction (CR) in lower organisms and mice. In 3T3‐L1 adipocytes, SRT and RSV inhibited PDE activities in membrane and cytosolic fractions. SRT inhibits rPDEs 1,2,3,4 but not rPDE5. SRT, RSV, Cilostamide (CIL) (PDE3 inhibitor), and rolipram (ROL) (PDE4 inhibitor), increased pAMPK, cAMP/PKA signaling, decreased acetylation of PGC1, and increased lipolysis. Phosphorylation of these signaling molecules was blocked by KT5720, a PKA inhibitor, but not by SiRNA‐mediated knockdown of EPAC. The EPAC agonist, 8‐pCPT‐2′‐O‐Me‐cAMP, did not increase the phosphorylation of AMPK or activate AMPK signaling. ROL had a relatively stronger effect on phosphorylation of PKA substrates than CIL, SRT and RSV, but smaller effects on phosphorylation of AMPK, and ACC, suggesting distinct cAMP pools involved in activation of AMPK. These and other results provide evidence that in adipocytes some effects of SRT and RSV may be related to their inhibition of PDEs and, thereby, alteration of intracellular cAMP concentrations, which may not be mediated by EPAC.