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Circulating Activators of Peroxisome Proliferator-Activated Receptors Are Reduced in Preeclamptic Pregnancy

Center for Reproductive Sciences, University of California San Francisco (L.L.W., R.N.T.), San Francisco, California 94143; and Division of Biological Sciences, Section of Ecology, Behavior, and Evolution, University of California San Diego (R.E.L.), San Diego, California 92093

Address all correspondence and requests for reprints to: Dr. Leslie Waite, Box 0556, San Francisco, California 94143. E-mail: lwaite{at}itsa.ucsf.edu.

We previously described activators of peroxisome proliferator-activated receptor (PPAR) in the serum of pregnant women. We have also characterized this activating component by using a hexane-extracted serum fraction to examine PPAR activator levels in normal and preeclamptic (PE) pregnancies. In this study we report that the pregnancy PPAR activator is present in similar concentrations in serum and plasma. We also found that the activating fractions from pregnancy sera stimulate not only PPAR, but also PPAR, 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 than PPAR 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.