When individuals undergo fasting, follow a very-low-carbohydrate diet, or have untreated type 1 diabetes, a class of compounds called ketone bodies are synthesized from acetyl-CoA produced by beta-oxidation in liver mitochondria. These compounds are beta-hydroxybutyrate, acetoacetate, and acetone. Ketone bodies are produced when insulin concentrations are very low and the rate of fatty acid oxidation produces acetyl-CoA faster than it can enter the citric acid cycle.

The resulting increase in acetyl-CoA concentrations in liver mitochondria causes two molecules of acetyl-CoA to be joined together, which begins the process of ketone body synthesis (also known as ketogenesis). As will be discussed later, the production of ketone bodies during a fast is an important metabolic adaptation, as it provides an alternative energy source for the brain that slows the catabolism and loss of body proteins.