The effects of fatty acids on acyl-CoA thioesterase activity and peroxisome proliferator-activated receptor gamma (PPARgamma), a regulator of lipid metabolism, were investigated in placental choriocarcinoma (BeWo) cells. Substrate preference for acyl-CoA thioesterase was in the following order; gamma-linolenoyol-CoA>/=arachidonoyol-CoAz.Gt;palmitoyl-CoA>/=linoleyol-CoA. However, when these cells were incubated with fatty acids, acyl-CoA thioesterase activity was increased by both conjugated linoleic and gamma linolenic acids, but not by docosahexaenoic and eicosapentaenoic acids. In addition, these fatty acids also increased expression of PPARgamma in these cells, suggesting a putative relationship between free fatty acid generated by acyl-CoA thioesterase and expression of PPARgamma. Since expression of PPARgamma is critical for feto-placental growth, these fatty acids may be important during pregnancy.