Figure 1

Endogenous and exogenous ketosis. Contrast between ketosis induced by starvation or high-fat diet (endogenous ketosis) and that generated by nutritional ketone ester ingestion (exogenous ketosis). Ketone bodies are endogenously produced in the liver from high circulating free fatty acids (FFA) from adipolysis. In contrast, nutritional ketone esters are cleaved in the gut and are absorbed through the gut epithelium and monocarboxylate transporters (MCT) into the circulation or undergo first-pass metabolism to ketone bodies in the liver. High concentrations of ketone bodies inhibit the nicotinic acid receptor (PUMA-G)-controlling adipolysis. Once released into the bloodstream, the ketones are metabolised by extrahepatic tissues in an identical fashion and being transported across the plasma and mitochondrial membranes by MCTs. D-β-Hydroxybutyrate (D-βHB) is converted to acetoacetate by D-β-hydroxybutyrate dehydrogenase (D-βHB DH) before entering the tricarboxylic acid (TCA) cycle as acetyl-CoA.