Increased fat degradation: The PKA-mediated phosphorylation and activation of HSL (see p. 189) and subsequent hydrolysis of stored fat (TAG) are enhanced by the elevated catecholamines norepinephrine and epinephrine. These hormones, which are secreted from the sympathetic nerve endings in adipose tissue and/or from the adrenal medulla, are physiologically important activators of HSL (Fig. 24.14, ).
2.
Increased fatty acid release: FA obtained from hydrolysis of TAG stored in adipocytes are primarily released into the blood (see Fig. 24.14, ). Bound to albumin, they are transported to a variety of tissues for use as fuel. The glycerol produced from TAG degradation is used as a gluconeogenic precursor by the liver, which contains glycerol kinase. [Note: FA can also be oxidized to acetyl CoA, which can enter the TCA cycle, thereby producing energy for the adipocyte. They also can be reesterified to glycerol 3-phosphate (from glyceroneogenesis, see p. 190), generating TAG and reducing plasma FA concentration.] 3.
Decreased fatty acid uptake: In fasting, LPL activity of adipose tissue is low. Consequently, FA in circulating TAG of lipoproteins are less available to adipose tissue than to muscle.
X. 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 (see p. 118). The lactate is used by the liver for gluconeogenesis (Cori cycle; see p. 118). 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 (see p. 183).]
A. Carbohydrate metabolism p. 97) 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. 24.15, 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; see p. 253).]
C. Protein metabolism