In order to protect blood glucose levels and depending on the metabolic needs, hepatic carbohydrate metabolism undergoes a shift from glucose storage via glucose uptake and glycogen synthesis during feeding towards glucose production via glycogenolysis and gluconeogenesis during fasting. In this way, the liver plays a central role in the adaptive response to fasting. During the first hours of fasting, glycemia is preserved by the process of glycogenolysis at the expense of liver glycogen reservoirs. During prolonged fasting, when glycogen stores become critically low, hepatic glucose production shifts to de novo glucose synthesis (gluconeogenesis) in order to maintain blood glucose levels. These metabolic changes are reflected in the expression and/or activity of hepatic enzymes. For example, prolonged fasting induces a decrease of the maximal activity of the glycolytic enzyme glucokinase and stimulates the expression of the gluconeogenic gene phosphoenolpyruvate carboxykinase (PEPCK). Simultaneously, the lipogenic enzymes acetyl-coenzyme A carboxylase and fatty acid synthase are suppressed and the activity of mitochondrial β-oxidation is enhanced. As a consequence, the hepatic carbon flux is directed towards gluconeogenesis and glucose output rather than glucose uptake
