A role for PPARα in hepatic inflammation has also been well established. PPARα null mice have a prolonged inflammatory response through the leukotriene B4 (LTB4) and its receptor compared to wild-type mice [47]. In fact LTB4 is a ligand of PPARα, that acts as an anti-inflammatory receptor stimulating LTB4 degradation in the β-oxidative pathways [48]. Moreover, activation of PPARα antagonizes NF-kB signalling, thus preventing the expression of several proinflammatory genes, such as C-reactive protein, fibrinogen –α and –β, acute-phase response proteins, serum amyloid A [49]. Therefore inhibition of PPARα transcriptional activity by acetaldehyde not only deranges the physiologic lipid metabolism leading to increased ROS and lipid peroxide production, but also stimulates the release of pro-inflammatory cytokines from hepatocytes.
