Biosynthesis of 15-deoxy-delta12,14-PGJ2 and the ligation of PPARgamma

J Clin Invest. 2003 Sep;112(6):945-55. doi: 10.1172/JCI18012.


15-deoxy-Delta12,14-PGJ2 (15d-PGJ2) has been identified as an endogenous ligand for PPARgamma, inducing adipogenesis in vitro. Additional roles for this molecule in the propagation and resolution of inflammation, ligation of NF-kappaB, and mediation of apoptosis have been proposed. However, quantitative, physiochemical evidence for the formation of 15d-PGJ2 in vivo is lacking. We report that 15d-PGJ2 is detectable using liquid chromatography-mass spectrometry-mass spectrometry at low picomolar concentrations in the medium of 3T3-L1 preadipocytes. However, despite induction of COX-2, production of PGs, including 15d-PGJ2, does not increase during adipocyte differentiation, a process unaltered by COX inhibition. 15d-PGJ2 is detectable as a minor product of COX-2 in human urine. However, its biosynthesis is unaltered during or after COX activation in vivo by LPS. Furthermore, the biosynthesis of 15d-PGJ2 is not augmented in the joint fluid of patients with arthritis, nor is its urinary excretion increased in patients with diabetes or obesity. 15d-PGJ2 is not the endogenous mediator of PPARgamma-dependent adipocyte activation and is unaltered in clinical settings in which PPARgamma activation has been implicated.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Adipocytes / cytology
  • Adipocytes / physiology
  • Aged
  • Aged, 80 and over
  • Animals
  • Arthritis / metabolism
  • Cell Differentiation / physiology
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Dinoprostone / metabolism
  • Female
  • Humans
  • Immunologic Factors / biosynthesis*
  • Immunologic Factors / chemistry
  • Immunologic Factors / urine
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Ligands
  • Male
  • Mass Spectrometry
  • Membrane Proteins
  • Mice
  • Middle Aged
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / chemistry
  • Prostaglandin D2 / metabolism*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Synovial Fluid / chemistry
  • Transcription Factors / metabolism*


  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Immunologic Factors
  • Isoenzymes
  • Ligands
  • Membrane Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • Dinoprostone
  • Prostaglandin D2