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

L Chastine Bell-Parikh1, Tomomi Ide, John A Lawson

  • 1Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104-6084, USA. garret@spirit.gcrc.upenn.edu

Insights

15-deoxy-Delta12,14-PGJ2 (15d-PGJ2) is detectable in vitro but not significantly produced in vivo during adipogenesis or inflammation. This study finds 15d-PGJ2 is not the primary mediator of PPARgamma-dependent adipocyte activation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2) is an endogenous PPARgamma ligand linked to adipogenesis and inflammation.
  • Proposed roles include NF-kappaB ligation and apoptosis mediation.
  • Quantitative in vivo evidence for 15d-PGJ2 formation is lacking.

Purpose of the Study:

  • To investigate the in vivo formation and physiological relevance of 15d-PGJ2.
  • To determine if 15d-PGJ2 mediates PPARgamma-dependent adipocyte activation.
  • To assess 15d-PGJ2 levels in conditions associated with inflammation and metabolic disease.

Main Methods:

  • Liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS) for 15d-PGJ2 detection.
  • Analysis of 15d-PGJ2 in 3T3-L1 preadipocyte cultures.
  • Measurement of 15d-PGJ2 in human urine and arthritis joint fluid.
  • Investigation of 15d-PGJ2 levels during COX-2 induction and LPS challenge.

Main Results:

  • 15d-PGJ2 is detectable at picomolar levels in vitro but not increased during adipocyte differentiation.
  • While a minor product of COX-2 in urine, its biosynthesis is not altered by LPS activation in vivo.
  • 15d-PGJ2 levels are not augmented in arthritis joint fluid, diabetes, or obesity.

Conclusions:

  • 15d-PGJ2 is not the endogenous mediator of PPARgamma-dependent adipocyte activation.
  • Its in vivo production and levels are not significantly altered in key physiological and pathological states.
  • The proposed roles of 15d-PGJ2 in inflammation and adipogenesis require further investigation regarding its in vivo significance.

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