Speaking of TZD's Ron Evans published a couple of papers in Cell fairly recently on endogenous ligands for PPARgamma. Here's one abstract:
Oxidized LDL regulates macrophage gene expression through ligand
activation of PPARgamma.
Nagy L, Tontonoz P, Alvarez JG, Chen H, Evans RM
The Salk Institute of Biological Studies, Howard Hughes Medical Institute, La Jolla, California 92037, USA.
Macrophage uptake of oxidized low-density lipoprotein (oxLDL) is thought to play a central role in foam cell formation and the
pathogenesis of atherosclerosis. We demonstrate here that oxLDL activates PPARgamma-dependent transcription through a
novel signaling pathway involving scavenger receptor-mediated particle uptake. Moreover, we identify two of the major oxidized
lipid components of oxLDL, 9-HODE and 13-HODE, as endogenous activators and ligands of PPARgamma. Our data suggest
that the biologic effects of oxLDL are coordinated by two sets of receptors, one on the cell surface, which binds and internalizes
the particle, and one in the nucleus, which is transcriptionally activated by its component lipids. These results suggest that
PPARgamma may be a key regulator of foam cell gene expression.
PMID: 9568715, UI: 98227666
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