When rodents were treated with PPARα ligands, the effects on gluconeogenesis were rather variable. In rats, G6Pase activity was not affected [31] whereas PEPCK expression levels were reduced [50] and LDHb levels were increased [45]. WY14643 feeding of mice had no effect on PC, PEPCK or G6Pase expression levels [7]. In a more informative study, mice were treated with fenofibrate and not only expression levels of individual enzymes but also gluconeogenic flux was analysed [30]. This flux was increased which was mirrored by increased expression of glycerol kinase (see also Section 3.3), but expression of PGC-1α, PEPCK and G6Pase was unaltered [30].Interestingly, the induction of the gluconeogenic genes PEPCK and G6Pase by the glucocorticoid dexamethasone was shown to be PPARα-dependent both in mice as well as in isolated human hepatocytes [51]. Lactate, being the dominant gluconeogenic precursor, and which is mainly derived from the Cori cycle, is transported into hepatocytes via the monocarboxylate transporter (MCT). Hepatic MCT-1 expression was shown to be upregulated by fasting, WY14643, fenofibrate and dietary PPARα agonists in mice and rats [52, 53], resulting in increased supply of gluconeogenic substrates.
