The findings in PPARα knockout mice make the picture even more confusing. Fasted PPARα −/− mice suffer from severe hypoglycemia starting already several hours after food withdrawal [3, 23]. During the first hours of fasting, blood glucose levels are mostly maintained by hepatic glycogenolysis. The steeper drop in blood glucose in PPARα −/− mice during early fasting, therefore, may reflect a reduced glycogen reserve or impaired liberation of glucose. Several groups reported that in the fed state hepatic glycogen stores were lower in PPARα −/− mice [3, 20, 21] compared to control mice, but no difference was observed in the fasted state [3, 20]. On the other hand, a study performed by Bandsma et al. [21] showed a reduced depletion of glycogen upon fasting (15 h or 24 h) concomitant with lower GP levels. According to several other groups, both hepatic glycogen storage in the fed state [25, 39] and glycogen depletion in response to fasting [20, 25, 39] were unaffected in PPARα −/− mice. It is not clear why opposing results were obtained by different investigators using the same mouse model.
