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

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

Research output: Contribution to journalArticle

287 Citations (Scopus)

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-PGJ 2 is not the endogenous mediator of PPARγ-dependent adipocyte activation and is unaltered in clinical settings in which PPARγ activation has been implicated.

Original languageEnglish
Pages (from-to)945-955
Number of pages11
JournalJournal of Clinical Investigation
Volume112
Issue number6
DOIs
Publication statusPublished - Sep 1 2003
Externally publishedYes

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Peroxisome Proliferator-Activated Receptors
Ligation
Adipocytes
Adipogenesis
Tandem Mass Spectrometry
Liquid Chromatography
Arthritis
9-deoxy-delta-9-prostaglandin D2
Obesity
Joints
Urine
Apoptosis
Ligands
Inflammation

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Bell-Parikh, L. C., Ide, T., Lawson, J. A., McNamara, P., Reilly, M., & FitzGerald, G. A. (2003). Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ. Journal of Clinical Investigation, 112(6), 945-955. https://doi.org/10.1172/JCI200318012

Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ. / Bell-Parikh, L. Chastine; Ide, Tomomi; Lawson, John A.; McNamara, Peter; Reilly, Muredach; FitzGerald, Garret A.

In: Journal of Clinical Investigation, Vol. 112, No. 6, 01.09.2003, p. 945-955.

Research output: Contribution to journalArticle

Bell-Parikh, LC, Ide, T, Lawson, JA, McNamara, P, Reilly, M & FitzGerald, GA 2003, 'Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ', Journal of Clinical Investigation, vol. 112, no. 6, pp. 945-955. https://doi.org/10.1172/JCI200318012
Bell-Parikh LC, Ide T, Lawson JA, McNamara P, Reilly M, FitzGerald GA. Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ. Journal of Clinical Investigation. 2003 Sep 1;112(6):945-955. https://doi.org/10.1172/JCI200318012
Bell-Parikh, L. Chastine ; Ide, Tomomi ; Lawson, John A. ; McNamara, Peter ; Reilly, Muredach ; FitzGerald, Garret A. / Biosynthesis of 15-deoxy-Δ12,14-PGJ2 and the ligation of PPARγ. In: Journal of Clinical Investigation. 2003 ; Vol. 112, No. 6. pp. 945-955.
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