Interestingly, it was suggested that the flux through the PPP was increased after fenofibrate treatment [30]. Indeed, expression levels of 6-phosphogluconate dehydrogenase (6PDGH), the rate-limiting enzyme of the oxidative branch of the PPP, and transaldolase 1 (Taldo1), a key enzyme for regulating flux from the triose phosphate pool through the nonoxidative limb of the pentose cycle, were augmented in fenofibrate treated mice [30] (Figure 2). This was in line with reduced levels of several PPP enzymes in PPARα −/− mice [35]. Furthermore, the reduced content of G6P in fenofibrate-treated mice is difficult to reconcile with an increased flux through gluconeogenesis (see below) and with reduced glycolysis (see above). Therefore, the hypothesis of increased rates of glucose oxidation through PPP is attractive. PPP remodeling of hepatic glucose metabolism upon PPARα activation may be important to provide NADPH needed to maintain the lipogenic flux, but may also support antioxidant action, since PPP is coupled to the synthesis of reduced gluthatione [41].
