Increased fat degradation is enhanced by the elevated catecholamines norepinephrine and epinephrine, which activate hormone-sensitive lipase (HSL) through PKA-mediated phosphorylation. This leads to the hydrolysis of stored fat (triglycerides) in adipose tissue. Norepinephrine and epinephrine are released from sympathetic nerve endings in adipose tissue and/or from the adrenal medulla. These hormones play a significant physiological role in activating HSL.

Fatty acids (FA) released from the hydrolysis of triglycerides in adipocytes are primarily released into the blood. They bind to albumin and are transported to various tissues to be used as fuel. The glycerol produced from the breakdown of triglycerides is used by the liver as a precursor for gluconeogenesis. It is important to note that fatty acids can also be oxidized to produce acetyl CoA, which can enter the TCA cycle and provide energy for the adipocyte. Alternatively, they can be reesterified to form triglycerides, thereby reducing the concentration of fatty acids in the blood plasma.

During fasting, the activity of lipoprotein lipase (LPL) in adipose tissue is low. This results in decreased availability of fatty acids from circulating triglycerides in lipoproteins to adipose tissue compared to muscle.

In resting skeletal muscle during fasting, there is a shift from glucose to fatty acids as the primary fuel source. However, during intense exercise, muscle initially uses creatine phosphate and its glycogen stores. As glycogen reserves are depleted, glucose 6-phosphate from glycogenolysis is converted to lactate through anaerobic glycolysis. The liver then utilizes lactate for gluconeogenesis in the Cori cycle. Once glycogen stores are further depleted, free fatty acids derived from the breakdown of triglycerides in adipose tissue become the dominant energy source for muscle. The rise in AMP during muscle contraction activates AMP-activated protein kinase (AMPK), which inactivates the muscle isozyme of acetyl-CoA carboxylase (ACC). This decreases malonyl CoA levels, allowing for fatty acid oxidation.

In fasting, the metabolism of carbohydrates and subsequent glucose metabolism in muscle is reduced due to low circulating insulin levels. As a result, the glucose produced by hepatic gluconeogenesis is unavailable for muscle and adipose tissue.

During early fasting, muscle utilizes fatty acids from adipose tissue and ketone bodies from the liver as fuel sources. However, as fasting continues, muscle decreases its utilization of ketone bodies, sparing them for the brain, and predominantly oxidizes fatty acids. The acetyl CoA produced from fatty acid oxidation indirectly inhibits pyruvate dehydrogenase (PDH) through the activation of PDH kinase. This leads to the sparing of pyruvate, which is transaminated to alanine and used by the liver for gluconeogenesis in the glucose-alanine cycle.

Protein metabolism is not discussed in this excerpt.
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