Human Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Metabolism of Carbohydrates and Lipids
Regulation of Lipid Metabolism and Tissue Energy Sources
The Economics of Carbohydrate and Lipid Metabolism in the Body – Fasting

In animals fed a carbohydrate-rich diet, the Oxidation of Fatty acids is suppressed. When an animal transitions from a well-fed state to starvation, the availability of glucose declines, and Liver Glycogen is mobilized to maintain Blood glucose levels. Consequently, blood Insulin concentrations drop, while Glucagon levels rise.

In adipose tissue, glucose utilization decreases and the inhibitory effect of insulin on lipolysis is reduced, leading to the mobilization of fat as free Fatty acids and glycerol. These free Fatty acids are transported to other Tissues, where they are either oxidized or esterified. Following activation (conversion to glycerol-3-phosphate), glycerol enters the carbohydrate pool (primarily in The Liver and Kidneys). During the transition from the fed state to fasting, endogenous glucose production (derived from Amino Acids and glycerol) lags behind its utilization and oxidation; liver glycogen stores become depleted, and blood glucose levels fall. Fat mobilization accelerates over the course of several hours, after which plasma free Fatty acid and blood glucose concentrations stabilize at levels characteristic of the fasting state (0.7–0.8 µmol∙mL^-1 and 60–70 mg/100 mL, respectively). It can be assumed that at this Blood Glucose Level, tissue supply matches the demands of utilization and oxidation. A compensatory upregulation of fatty acid and ketone body oxidation helps reduce glucose oxidation rates. This delicate equilibrium can be disrupted by an increased demand for glucose or impaired utilization processes, in which case further fat mobilization is triggered. Providing the body with glycerol is a crucial function of adipose tissue, as this serves as the sole carbohydrate source (along with CARBOHYDRATES derived from Proteins via Gluconeogenesis) capable of supplying the fasting Organism with the glucose required for metabolic processes that exclusively rely on glucose as a substrate. In humans undergoing prolonged starvation, protein-derived gluconeogenesis declines due to reduced amino acid release from Muscles, particularly Alanine. This coincides temporally with Brain adaptation, enabling the brain to compensate for roughly 50% of its glucose oxidation needs through The oxidation of Ketone Bodies.

The feedback regulation of free fatty acid release from adipose tissue during fasting can occur through the direct action of ketone bodies and free fatty acids on the Pancreas, resulting in increased insulin production. The mobilization of free fatty acids typically exceeds the metabolic demands of oxidation, as a significant fraction of these acids undergoes Esterification even during periods of starvation. Because hepatocytes take up and esterify a large portion of free fatty acids, the liver plays a regulatory role by clearing excess free fatty acids from the Circulation. When the body receives an adequate supply of carbohydrates, the majority of hepatic free fatty acids are esterified, eventually transported out of the liver as VLDL, and utilized by extrahepatic tissues. However, an increased influx of free fatty acids can activate an alternative pathway—ketogenesis—enabling the liver to continue redistributing the bulk of the absorbed fatty acids in a form readily usable by extrahepatic tissues.

Most of the discussed mechanisms are illustrated in Fig. 28.8. It should be noted that a carbohydrate cycle operates, which includes the release of glycerol from adipose tissue, its conversion into glucose in the liver, and The transport of the latter back to adipose tissue. Another cycle, the lipid cycle, involves the release of free fatty acids from adipose tissue, their transport to the liver, esterification, and return to adipose tissue as VLDL.

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