Although contributing only 2% of the adult weight, the brain accounts for a consistent 20% of the basal O2 consumption of the body at rest. Because the brain is vital to the proper functioning of all organs of the body, special priority is given to its fuel needs. To provide energy, substrates must be able to cross the endothelial cells that line the blood vessels in the brain (the blood–brain barrier [BBB]). In the fed state, the brain exclusively uses glucose as a fuel (GLUT-1 of the BBB is insulin independent), completely oxidizing ~140 g/day to carbon dioxide and water. Because the brain contains no significant stores of glycogen, it is completely dependent on the availability of blood glucose (Fig. 24.8, ). [Note: If blood glucose levels fall to <50 mg/dl (normal fasted blood glucose is 70–99 mg/dl), cerebral function is impaired (see p. 315).] The brain also lacks significant stores of TAG, and the FA circulating in the blood make little contribution to energy production for reasons that are unclear. The intertissue exchanges characteristic of the absorptive period are summarized in Figure 24.9.
VII. OVERVIEW OF THE FASTED STATE
Fasting begins if no food is ingested after the absorptive period. It may result from an inability to obtain food, the desire to lose weight rapidly, or clinical situations in which an individual cannot eat (for example, because of trauma, surgery, cancer, or burns). In the absence of food, plasma levels of glucose, amino acids, and TAG fall, triggering a decline in insulin secretion and an increase in glucagon, epinephrine, and cortisol secretion. The decreased insulin/counterregulatory hormone ratio and the decreased availability of circulating substrates make the postabsorptive period of nutrient deprivation a catabolic period characterized by degradation of TAG, glycogen, and protein. This sets into motion an exchange of substrates among the liver, adipose tissue, skeletal muscle, and brain that is guided by two priorities: 1) the need to maintain adequate plasma levels of glucose to sustain energy metabolism in the brain, red blood cells, and other glucose-requiring tissues and 2) the need to mobilize FA from TAG in WAT for the synthesis and release of ketone bodies by the liver to supply energy to other tissues and spare body protein. As a result, blood glucose levels are maintained within a narrow range in fasting, while FA and ketone body levels increase. [Note: Maintaining glucose requires that the substrates for gluconeogenesis (such as pyruvate, alanine, and glycerol) be available.]
A. Fuel stores
The metabolic fuels available in a normal 70-kg man at the beginning of a fast are shown in Figure 24.10. Observe the enormous caloric stores available in the form of TAG compared with those contained in glycogen. [Note: Although protein is listed as an energy source, each protein also has a function unrelated to energy metabolism (for example, as a structural component of the body or as an enzyme). Therefore, only about one third of the body’s protein can be used for energy production without fatally compromising vital functions.]
B. Enzymic changes