Resting Skeletal Muscle in Fasting

Resting muscle switches from glucose to FA as its major fuel source in fasting. [Note: By contrast, exercising muscle initially uses creatine phosphate and its glycogen stores. During intense exercise, glucose 6-phosphate from glycogenolysis is converted to lactate by anaerobic glycolysis . The lactate is used by the liver for gluconeogenesis . As these glycogen reserves are depleted, free FA provided by the degradation of TAG in adipose tissue become the dominant energy source. The contraction-based rise in AMP activates AMPK that phosphorylates and inactivates the muscle isozyme of ACC, decreasing malonyl CoA and allowing FA oxidation .]
A. Carbohydrate metabolism
Glucose transport into skeletal myocytes via insulin-sensitive GLUT-4  and subsequent glucose metabolism are decreased because circulating insulin levels are low. Therefore, the glucose from hepatic gluconeogenesis is unavailable to muscle and adipose.
B. Lipid metabolism
Early in fasting, muscle uses FA from adipose tissue and ketone bodies from the liver as fuels (Fig. 1, and ). In prolonged fasting, muscle decreases its use of ketone bodies (thus sparing them for the brain) and oxidizes FA almost exclusively. [Note: The acetyl CoA from FA oxidation indirectly inhibits PDH (by activation of PDH kinase) and spares pyruvate, which is transaminated to alanine and used by the liver for gluconeogenesis
(glucose–alanine cycle).]

Figure 1:  Major metabolic pathways in skeletal muscle during fasting. [Note: The numbers in the circles, which appear both in the figure and in the corresponding citation in the text, indicate important pathways for fat or protein metabolism.] CoA = coenzyme A; TCA = tricarboxylic acid.
C. Protein metabolism
During the first few days of fasting, there is a rapid breakdown of muscle protein (for example, glycolytic enzymes), providing amino acids that are used by the liver for gluconeogenesis (see Fig. 1, ). Because muscle does not have glucagon receptors, muscle proteolysis is initiated by a fall in insulin and sustained by a rise in glucocorticoids. [Note: Alanine and glutamine are quantitatively the most important glucogenic amino acids released from muscle. They are produced by the catabolism of BCAA . The glutamine is used as a fuel by enterocytes, for example, which send out alanine that is used in hepatic gluconeogenesis (glucose–alanine cycle)]. In the second week of fasting, the rate of muscle proteolysis decreases, paralleling a decline in the need for glucose as a fuel for the brain, which has begun using ketone bodies as a source of energy.