Metabolomics of the effect of AMPK activation by AICAR on human umbilical vein endothelial cells

Int J Mol Med. 2012 Jan;29(1):88-94. doi: 10.3892/ijmm.2011.802. Epub 2011 Sep 28.


AMP-activated protein kinase (AMPK) is a metabolic master switch expressed in a great number of cells and tissues. AMPK is thought to modulate the cellular response to different stresses that increase cellular AMP concentration. The adenosine analog, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) is an AMPK activator used in many studies to assess the effects of AMPK activation on cellular metabolism and function. However, the effect of AICAR on cell metabolism reaches many different pathways and metabolites, some of which do not seem to be fully related to AMPK activation. We have now for the first time used NMR metabolomics on human umbilical vein endothelial cells (HUVEC) for the study of the global metabolic impact of AMPK activation by AICAR. In our study, incubation with AICAR activates AMPK and is associated with, among others, broad metabolic alterations in energy metabolism and phospholipid biosynthesis. Using NMR spectroscopy and metabolic network tools, we analyzed the connections between the different metabolic switches activated by AICAR. Our approach reveals a strong interconnection between different phospholipid precursors and oxidation by-products. Metabolomics profiling is a useful tool for detecting major metabolic alterations, generating new hypotheses and provides some insight about the different molecular correlations in a complex system. The present study shows that AICAR induces metabolic effects in cell metabolism well beyond energy production pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Analysis of Variance
  • Cells, Cultured
  • Citric Acid Cycle / drug effects
  • Enzyme Activation / drug effects
  • Glycolysis / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / enzymology*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Metabolic Networks and Pathways / drug effects
  • Metabolome
  • Metabolomics / methods*
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Phospholipids / metabolism
  • Ribonucleosides / pharmacology*


  • Phospholipids
  • Ribonucleosides
  • Aminoimidazole Carboxamide
  • acadesine
  • AMP-Activated Protein Kinases