Furthermore, there are examples of PPAR activation affecting brain function via their systemic metabolic effects. Oleoylethanolamide is an endogenous lipid mediator that is released when fat enters the small intestine, and it induces satiety via PPARα in the gut (Fu et al., 2003). Administration of oleoylethanolamide improves memory retention in rats by acting as a PPARα agonist and facilitating memory consolidation through noradrenergic activation of the basolateral amygdala, a mechanism involved in memory enhancement (Campolongo et al., 2009). Also, this lipid mediator restores gut-stimulated dopamine release in a PPARα-dependent manner and eliminates motivation deficits in mice consuming a high-fat diet (Tellez et al., 2013). Thus, lipid/PPAR signaling in the periphery may regulate central behaviors.
