The Fed and Fasting States

We derive our energy and build our cells and tissues using energy derived from the metabolic breakdown of three major classes of nutrients; carbohydrates (simple and complex sugars), lipids (various fats and oils), and protein (very large nitrogen containing molecules found in plant and animal tissues; meat is the clearest representative.)

We will consider each of these three classes of nutrient and the role of the liver in their metabolism in two different states, "fed" and "fasting." The fed state refers to the period following a meal and is characterized by high levels of nutrients in the blood. There are high circulating levels of a family of simple sugars, the most important being glucose. In addition, typically there are high levels of fat packaged in relatively large (but not visible to naked eye) structures called chylomicrons. A chylomicron is composed of a small droplet of fat (triglyceride) at its center surrounded by a family of detergent- like molecules and protein that make the structure stable in the aqueous (water based) environment of the blood. Finally there are relatively high levels of amino acids derived from the

breakdown of protein in the diet.

During a several hour period following a meal, there is a progressive shift to the fasting state as the various nutrients are taken up by cells for storage, the synthesis of needed cell components, and for use as fuel in the production of energy to support a broad range of cellular processes. Thus fed and fasting are not distinct states, but rather represent two ends of a continuum. As the fasting state becomes more established, the blood levels of glucose, fat, and amino acids progressively fall.

The fed state is signaled by the presence of high levels of insulin, an important endocrine system hormone secreted in response to high blood sugar levels. The major signal indicating that the body is fasting is provided when blood glucose levels fall to a low level and there is resulting fall in the circulating level of insulin. Low levels of insulin, accompanied by elevated levels of other hormone signals such as glucogon, provide a signal that the circulating level of fuels in the blood are inadequate. The body responds

by releasing free fatty acids from fat stored in specialized cells known as adipose cells making up the fatty tissue of the body. At the same time the liver begins to make glucose available to the body by synthesizing and by producing free glucose from storage. This glucose is released to the blood for use by other tissues. Similarly, amino acids are produced by the onset of protein degradation in many tissues, primarily muscle, for use within the cell in the synthesis of new needed protein or fuel. Amino acid that is not used by the cell is released to the blood and taken up by the liver as a source of carbon molecules in the synthesis of glucose.

Given adequate fluid intake, the body is able to maintain the fasting state so long as fat stores exist, a period of approximately 10-15 weeks in an initially well nourished adult. Once the fat reserves are exhausted, starvation begins and there is a rapid loss of protein as the body invades the structural components of cells for needed fuel. Starvation progresses quickly to death as proteins needed for critical activities of cells are degraded and the ability of the body to maintain itself is compromised.