Transcript levels of key gluconeogenic enzymes were not uniformly altered in PPARα knockout mice. PEPCK expression levels were shown to be similarly induced upon fasting in wild-type and PPARα −/− mice [3, 22], which suggests that PEPCK is upregulated by fasting in a PPARα independent manner. Yet, lower expression of PEPCK in 24 hours fasted [21] and refed [20] PPARα −/− mice in comparison with control animals was reported as well. G6Pase and G6P translocase were not differently expressed between fed PPARα −/− and wild type mice, but induction upon fasting of these two enzymes was impaired in PPARα −/− mice [21]. Furthermore, a severe decrease in expression of LDH and PC was found in PPARα −/− mice [4, 35], which suggests impaired gluconeogenesis from lactate. However, most groups reported normal plasma lactate levels in PPARα −/− mice [20, 21, 25]. This suggests a supportive role for PPARα in the gluconeogenic response to fasting (Figure 2).
