The inverse relationship of many gene responses to Wy-14,643 and to Cyp1b1 deletion (Table 3, Figure 6C) points to extensive suppression of their endogenous regulation by PPARα. Some genes (Cyp4a forms) are also substantially suppressed in PPARα-ko livers, indicative of endogenous PPARα stimulation [44]. Others (CD36) are more suppressed in Cyp1b1-ko mice, possibly due to the additional suppression of PPARγ (Tables 2 and 3). Much shorter exposures to Wy-14,643 targeted several additional PPARα-responsive genes that exhibit inverse responses to Cyp1b1 deletion (Tables 2 and 3) [58]. These metabolic genes often exhibit circadian fluctuation and rapid turnover that benefit from a shorter agonist exposure [65].
