A number of studies were conducted in which PPARα agonists were administered to rodents after which glycogen content, glycogen metabolizing enzyme expression, and/or fluxes were monitored. In all cases, a reduction of hepatic glycogen storage was seen but the proposed underlying mechanisms are rather contradictory. In mice maintained on a diet containing ciprofibrate or fenofibrate, lower hepatic glycogen stores [25, 30] were accompanied by lower hepatic G6P content [30], which is both the precursor in glycogen synthesis and the end product of glycogen breakdown. According to Oosterveer et al., there was both an increased flux of glycogen synthesis through Gys-2 and an increased flux of glycogen breakdown through GP [30]. In contrast, clofibrate treatment of rats reduced both Gys-2 and GP activity, resulting in reduced hepatic glycogen content, however, without altering hepatic G6P levels [31]. In yet another study, treatment of rats with WY14643 did not alter Gys-2 expression, but did decrease GP expression levels [45]. Unfortunately, in none of these studies Gys-2 expression, glycogen levels, and glycogenic flux were studied simultaneously in the same model.
