It is not clear why both after PPARα activation and PPARα depletion glycolytic enzyme levels are suppressed. In fact, both the long-term deletion of this transcription factor, which might install a new metabolic homeostasis, as the long-term activation of PPARα using synthetic high affinity agonists, are nonphysiological conditions and the results have to be interpreted with care. Refeeding is expected to induce glycolytic enzymes in response to insulin signaling. This was not the case in PPARα deficient mice, possibly indicating that PPARα −/− hepatocytes are insulin resistant (see also below).
