Molecular Medicine

, Volume 17, Issue 9–10, pp 1022–1030 | Cite as

Small-Molecule Activators of AMP-Activated Protein Kinase (AMPK), RSVA314 and RSVA405, Inhibit Adipogenesis

  • Valérie Vingtdeux
  • Pallavi Chandakkar
  • Haitian Zhao
  • Peter Davies
  • Philippe Marambaud
Research Article


AMP-activated protein kinase (AMPK) is a sensor and regulator of cellular energy metabolism potentially Implicated In a broad range of conditions, including obesity and Alzheimer’s disease. Its role in the control of key metabolic enzymes makes this kinase a central player in glucose and lipid homeostasis. Recently, by screening a library of synthetic small molecules selected for their structural similarity with the natural polyphenol resveratrol, we identified RSVA314 and RSVA405 as potent indirect activators of AMPK (half-maximal effective concentration (EC50) = 1 µmol/L in cell-based assays). Here we show that RSVA314 and RSVA405 can significantly activate AMPK and inhibit acetyl-CoA carboxylase (ACC), one target of AMPK and a key regulator of fatty acid biogenesis, in nondifferentiated and proliferating 3T3-L1 adipocytes. We found that RSVA314 and RSVA405 treatments inhibited 3T3-L1 adipocyte differentiation by interfering with mitotic clonal expansion during preadipocyte proliferation (halfmaximal inhibitory concentration (IC50) = 0.5 µmol/L). RSVA314 and RSVA405 prevented the adipogenesis-dependent transcriptional changes of multiple gene products involved in the adipogenic process, including peroxisome proliferator-activated receptor (PPAR)-γ, CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase, fatty acid binding protein 4 (aP2), RANTES or resistin. Furthermore, orally administered RSVA405 at 20 and 100 mg/kg/d significantly reduced the body weight gain of mice fed a high-fat diet. This work shows that the novel small-molecule activators of AMPK (RSVA314 and RSVA405) are potent inhibitors of adipogenesis and thus may have therapeutic potential against obesity.



This work was supported in part by the National Institutes of Health (grant PO1 AT004511; National Center for Complementary and Alternative Medicine [NCCAM] Project 2 to P Marambaud).


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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Valérie Vingtdeux
    • 1
  • Pallavi Chandakkar
    • 1
  • Haitian Zhao
    • 1
  • Peter Davies
    • 1
    • 2
  • Philippe Marambaud
    • 1
    • 2
  1. 1.Litwin-Zucker Research Center for the Study of Alzheimer’s DiseaseThe Feinstein Institute for Medical ResearchManhassetUSA
  2. 2.Department of PathologyAlbert Einstein College of MedicineBronxUSA

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