It was shown that PPARα has an important modulatory function on hepatic insulin action through its target TRB3, the mammalian tribbles homolog. During fasting and upon WY14643 treatment, hepatic expression of TRB3 was induced in wild type, but not in PPARα −/− mice [57]. TRB3 disrupts insulin signaling by interfering with activation of Akt [58]. The PPARα-mediated induction of TRB3 was proposed to suppress insulin action, to induce insulin resistance, and subsequently to promote gluconeogenesis [57].
