Two hours after a meal, the blood glucose level is diminished slightly, and tissues receive glucose released from liver glycogen. There is little or no synthesis of TAGs. By four hours after a meal, blood glucose has fallen further, insulin secretion has slowed, and glucagon secretion has increased. These hormonal signals mobilize TAGs from adipose tissue, which now become the primary fuel for muscle and liver.

To provide glucose for the brain, the liver degrades certain proteins—those most expendable in an organism not ingesting food. Their nonessential amino acids are transaminated or deaminated, and the extra amino groups are converted to urea, which is exported via the bloodstream to the kidneys and excreted in the urine.

Also in the liver, and to some extent in the kidneys, the carbon skeletons of glucogenic amino acids are converted to pyruvate or intermediates of the citric acid cycle. These intermediates (as well as the glycerol derived from TAGs in adipose tissue) provide the starting materials for gluconeogenesis in the liver, yielding glucose for export to the brain.

Fatty acids released from adipose tissue are oxidized to acetyl-CoA in the liver, but as oxaloacetate is depleted by the use of citric acid cycle intermediates for gluconeogenesis, entry of acetyl-CoA into the cycle is inhibited and acetyl-CoA accumulates. This favors the formation of acetoacetyl-CoA and ketone bodies. After a few days of fasting, the levels of ketone bodies in the blood rise as they are exported from the liver to the heart, skeletal muscle, and brain, which use these fuels instead of glucose.