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This version published online on November 23, 2004
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-0849
A more recent version of this article appeared on February 1, 2005
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Submitted on May 5, 2004
Accepted on November 14, 2004

Circulating Activators of PPARs are Reduced in Preeclamptic Pregnancy

Leslie L. Waite*, Rachel E. Louie, and Robert N. Taylor

University of California San Francisco Center for Reproductive Sciences; University of California San Diego Division of Biology, Department of Ecology, Behavior, and Evolution

* To whom correspondence should be addressed.
Leslie L. Waite, E-mail: lwaite{at}itsa.ucsf.edu

We previously described activators of Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) in the serum of pregnant women. We have further characterized this activating component by using a hexane-extracted serum fraction to examine PPAR activator levels in normal and preeclamptic (PE) pregnancies. Here we report that the pregnancy PPAR activator is present in similar concentrations in both serum and plasma. We also found that the activating fractions from pregnancy sera stimulate not only PPAR{gamma}, but also PPAR{alpha}, and are capable of inhibiting the production of inflammatory cytokines, consistent with known PPAR ligands. In experiments comparing extracts from normal and PE patients, we found that extracts from women with severe PE showed a reduced level of PPAR activation compared with extracts from normal pregnant women. This reduction was more pronounced for PPAR{gamma} than PPAR{alpha} activation. Finally, this reduction in circulating PPAR activator was observed weeks and sometimes months before the clinical diagnosis of PE.

Based on these results, we conclude that PPAR activation is reduced in preeclamptic pregnancy before the onset of maternal symptoms. We speculate that endogenous regulators of PPAR play a role in maternal metabolism and immune function in normal and pathological pregnancies.


Key words: PPAR • preeclampsia • inflammation • trophoblast • placenta







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