Resting Skeletal Muscle in Fasting

RESTING SKELETAL MUSCLE IN FASTING

Resting muscle switches from glucose to FAs as its major fuel source in fasting. [Note: By contrast, exercising muscle initially uses its glycogen stores as a source of energy. During intense exercise, glucose 6-phosphate derived from glycogen is converted to lactate by anaerobic glycolysis. The lactate is used by liver for gluconeogenesis (Cori cycle;). As these glycogen reserves are depleted, free FAs provided by the mobilization of TAG from 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 muscle cells via insulin-sensitive GLUT-4 and subsequent glucose metabolism are depressed because of low levels of circulating insulin. Therefore, the glucose from hepatic gluconeogenesis is unavailable to muscle (and adipose tissue).

B. Lipid metabolism

During the first 2 weeks of fasting, muscle uses FA from adipose tissue and ketone bodies from the liver as fuels (Figure 24.15, 1 and 2 ). After about 3 weeks of fasting, muscle decreases its use of ketone bodies (thus sparing them for 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 liver for gluconeogenesis (glucose–alanine cycle;).]

C. Protein metabolism

During the first few days of fasting, there is a rapid breakdown of muscle protein, providing amino acids that are used by the liver for gluconeogenesis (see Figure 24.15, 3 ). 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 gluconeogenic amino acids released from muscle. They are produced by the catabolism of BCAAs.] The glutamine is used as a fuel by enterocytes, for example, which send out alanine that is used in hepatic gluconeogenesis. 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.

Figure 24.15 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.