explained by immune cells expressing both PPARγ and PPARδ receptors and each receptor having different thresholds for activation by rosiglitazone (Sakamoto et al., 2000; Gordon and Martinez, 2010). Additionally, the PPARγ-independent actions of these agonists likely result from their ability to directly target mitochondria and also activate other PPAR receptors (Sakamoto et al., 2000; Colca et al., 2004; Paddock et al., 2007; Orasanu et al., 2008; Geldenhuys et al., 2011). Evidence of receptor-dependent and independent effects, especially within the same animal, provides strong support for the diverse nature of the beneficial effects of PPAR agonists.
