PPAR agonists induced both up- and down-regulated genes in the amygdala, PFC and liver. Many of these genes have not been previously implicated in PPAR actions, including some that are regulated by all three PPAR agonists in multiple tissues and contain a PPAR response element in the promoter region (e.g., Dbp, Gm129 and Tsc22d3). Therefore this study reveals potentially novel PPAR agonist targets which may be relevant for other pathological conditions. Because bezafibrate is a pan-PPAR agonist, we expected it to produce the greatest number of gene expression changes, especially considering that the PPARβ/δ subunit is the most abundant isotype in brain 35. However, beza produced the fewest expression changes in all tissues studied, while feno produced the most changes in amygdala and PFC, and tesa produced the most changes in liver. These findings are consistent with the behavioral results showing that bezafibrate was ineffective while fenofibrate and tesaglitazar decreased alcohol consumption.
