Given the important role of PPARα in the adaptive response to fasting, it is conceivable that activated PPARα directly regulates or indirectly influences the expression or activity of some key gluconeogenic genes. Several in vitro studies have been conducted to test whether gluconeogenic genes such as PEPCK, G6Pase, and cytosolic glycerol 3-phosphate dehydrogenase (cGPDH) are potential PPARα target genes. After discussion of the hypoglycemic phenotype of PPARα −/− mice, the general gluconeogenic pathway and gluconeogenesis from the major substrates lactate/pyruvate will be reviewed, whereafter glucose synthesis from the minor substrates glycerol and alanine are discussed.
