PPAR agonists have been extensively studied for their role in modulating metabolism and energy production (Alaynick, 2008; Sugden et al., 2009). Activation of PPAR receptors by fatty acids promotes mitochondrial β-oxidation allowing for greater cellular energy production (Gulick et al., 1994). Many of the effects of PPARs on bioenergetics occur through regulation of gene expression. Specifically, activation of PPARδ increases production of mTFA (mitochondrial transcription factor), UCPs (uncoupling proteins) 2 and 3 (UCP2/3), and lipoprotein lipase (Muoio et al., 2002; Dressel et al., 2003; Jiang et al., 2010). Similarly, PPARα activation increases the transport and utilization of fatty acids needed during β-oxidation and PPARγ activation increases cytochrome c oxidase 6A2 (Desvergne and Wahli, 1999; Allen et al., 2006). Activation of PPARγ also induces the expression of lipoprotein lipase and stimulates mitochondrial biogenesis (Strum et al., 2007; Benedusi et al., 2012; Morino et al., 2012). Further, PPARγ activation stabilizes existing mitochondria and prevents their dysfunction (Fuenzalida et al., 2007; Quintanilla et al., 2008). These effects may underlie the increased mitochondrial energy production observed following administration of PPARγ agonists in models of CNS insult (Hunter et al., 2007; Sauerbeck et al., 2011).
