AMPK inhibits fatty acid-induced increases in NF-kappaB transactivation in cultured human umbilical vein endothelial cells

Biochem Biophys Res Commun. 2004 Nov 26;324(4):1204-9. doi: 10.1016/j.bbrc.2004.09.177.


The fuel sensing enzyme AMP-activated protein kinase (AMPK) enhances processes that generate ATP when stresses such as exercise or glucose deprivation make cells energy deficient. We report here a novel role of AMPK, to prevent the activation of NF-kappaB in endothelial cells exposed to the fatty acid palmitate or the cytokine TNF-alpha. Incubation of cultured human umbilical vein endothelial cells (HUVEC) with elevated levels of palmitate (0.4mM) increased NF-kappaB reporter gene expression by 2- to 4-fold within 8h and caused a 7-fold increase in VCAM-1 mRNA expression at 24h. In contrast, no increase in reporter gene expression was detected for AP-1, glucocorticoid-, cyclic AMP-, or serum response elements. Similar increases in NF-kappaB activation and VCAM-1 expression were not observed in cells incubated with an elevated concentration of glucose (25mM). The increases in NF-kappaB activation and VCAM-1 expression caused by palmitate were markedly inhibited by co-incubation with the AMPK activator AICAR and, where studied, by expression of a constitutively active AMPK. Likewise, AMPK activation inhibited the increase in NF-kappaB reporter gene expression observed in HUVEC incubated with TNF-alpha. The results suggest that AMPK inhibits the activation of NF-kappaB caused by both palmitate and TNF-alpha. The mechanism responsible for this action, as well as its relevance to the reported anti-atherogenic actions of exercise, metformin, thiazolidinediones, and adiponectin, all of which have been shown to activate AMPK, remains to be determined.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Multienzyme Complexes / physiology*
  • NF-kappa B / antagonists & inhibitors*
  • Palmitates / antagonists & inhibitors*
  • Polymerase Chain Reaction
  • Protein-Serine-Threonine Kinases / physiology*
  • RNA, Messenger / biosynthesis
  • Transcriptional Activation*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Umbilical Veins / cytology
  • Vascular Cell Adhesion Molecule-1 / biosynthesis
  • Vascular Cell Adhesion Molecule-1 / genetics


  • Multienzyme Complexes
  • NF-kappa B
  • Palmitates
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases