AMPK-sensed cellular energy state regulates the release of extracellular Fatty Acid Synthase

Biochem Biophys Res Commun. 2009 Jan 16;378(3):488-93. doi: 10.1016/j.bbrc.2008.11.067. Epub 2008 Nov 24.


Fatty Acid Synthase (FASN), a 250-kDa cytosolic multi-enzyme catalyzing eukaryotic de novo FA biogenesis, unexpectedly localizes in cancer cell culture supernatants and in the blood of cancer patients. High levels of "extracellular FASN" have recently been found in supernatants from Hepatitis C Virus-infected liver cells. The ultimate mechanism regulating FASN release, however, remained completely undefined. When the AMPK-activating drug AICAR was used to simulate an elevated AMP/ATP ratio in breast cancer cells, ELISA-based analyses revealed that extracellular FASN dramatically augmented in a dose- and time-dependent manner. Immunoblotting procedures using a battery of anti-FASN antibodies further confirmed that, in response to AMPK activation, FASN protein is depleted from the cytosol to accumulate as different FASN isoforms in the extracellular milieu. siRNA-induced blockade of AMPK expression largely attenuated AICAR-promoted FASN release. FASN release might represent a previously unrecognized mechanism through which AMPK monitor and restores cellular energy state in response to increasing AMP/ATP ratios.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Adenosine Monophosphate / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Antibodies, Monoclonal / immunology
  • Cell Line, Tumor
  • Culture Media, Conditioned
  • Cytosol / enzymology
  • Energy Metabolism
  • Fatty Acid Synthase, Type I / antagonists & inhibitors
  • Fatty Acid Synthase, Type I / immunology
  • Fatty Acid Synthase, Type I / metabolism*
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / immunology
  • Isoenzymes / metabolism
  • Neoplasms / enzymology
  • RNA, Small Interfering / genetics
  • Ribonucleotides / pharmacology


  • Antibodies, Monoclonal
  • Culture Media, Conditioned
  • Isoenzymes
  • RNA, Small Interfering
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Adenosine Monophosphate
  • Adenosine Triphosphate
  • FASN protein, human
  • Fatty Acid Synthase, Type I
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide