Apart from a direct effect on glycogen metabolizing enzymes, PPARα may indirectly affect the fate of newly formed G6P which is either used in glycolysis, for transfer to plasma as glucose, for glycogen synthesis or to enter the PPP pathway (Figure 1). Normally, insulin directs newly formed G6P towards glycogen disposition. According to Sugden et al., PPARα deficiency resulted in impaired insulin action (see also below) with respect to net hepatic glycogen disposition starting from G6P on refeeding after starvation [39], resulting in slower repletion of glycogen stores. In sharp contrast, as mentioned above, it was shown by performing flux studies with stable isotopes that newly synthesized G6P was partitioned away from plasma glucose towards glycogen synthesis in PPARα knockout mice [21]. These two lines of observations are mutually exclusive. However, the observation of reduced glycogen repletion upon refeeding and reduced Gys-2 expression levels in PPARα −/− mice is consistent between the different studies, pointing to an important role of PPARα in the control of glycogen synthesis (Figure 3).
