Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ
L. Chastine Bell-Parikh, … , Muredach Reilly, Garret A. FitzGerald
L. Chastine Bell-Parikh, … , Muredach Reilly, Garret A. FitzGerald
Published September 15, 2003
Citation Information: J Clin Invest. 2003;112(6):945-955. https://doi.org/10.1172/JCI18012.
View: Text | PDF
Article Cell biology

Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ

  • Text
  • PDF
Abstract

15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) has been identified as an endogenous ligand for PPARγ, inducing adipogenesis in vitro. Additional roles for this molecule in the propagation and resolution of inflammation, ligation of NF-κB, 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 PPARγ-dependent adipocyte activation and is unaltered in clinical settings in which PPARγ activation has been implicated.

Authors

L. Chastine Bell-Parikh, Tomomi Ide, John A. Lawson, Peter McNamara, Muredach Reilly, Garret A. FitzGerald

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
15d-PGJ2 in human urine. (a) Mass chromatogram of 15d-PGJ2 in human urin...
15d-PGJ2 in human urine. (a) Mass chromatogram of 15d-PGJ2 in human urine. Representative chromatogram obtained by NI-ESI- MRM. Healthy human volunteers abstained from NSAID use for more than 5 days before urine collection. Asterisks denote isomers of [2H4]15d-PGJ2 present in the internal standard. The major detectable isomer is identified by shading (b) Formation of 15d-PGJ2 by dehydration of PGJ2 or PGD2. Unlabeled PGD2 or PGJ2 (0.2 ng/ml) was added to human urine at T = 0 hour. Aliquots (5.0 ml) were analyzed at the indicated time points for loss of spike and concomitant formation of 15d-PGJ2. The numbers above bars represent amount (%) of added PG remaining at the corresponding time point. (c) Failure to detect endogenous PGJ2 in freshly voided urine. Representative chromatogram of PGJ2 in urine. NI-ESI- MRM of urine samples (5.0 ml + 1.0 ng [18O2]-PGJ2) that were SPE extracted within 15 minutes of voiding. HPLC mobile phase was 30% CH3CN (isocratic). Other parameters were identical to those used for 15d-PGJ2. The PGJ2 peak is shaded. Estimation of the threshold of PGJ2 detection was based on the least integratable peak.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts