Several different mechanisms were put forward to explain the fasting-induced hypoglycemia in PPARα −/− mice, some of which may be operative simultaneously. Some researchers believe this is mainly due to hepatic defects including liver glycogen depletion [3, 18], a blunted gluconeogenic response [18–20, 22, 24], reduced FAO rates [3, 18, 20, 25] and/or stronger inhibition of hepatic glucose output due to partitioning of G6P away from blood glucose [21]. Others blame increased glucose utilization in extrahepatic tissues [3, 20, 23, 35]. In favour of the last option is the fact that hepatic reexpression of PPARα did not rescue the metabolic phenotype of PPARα −/− mice [23].
