Real-time Detection of Hepatic Gluconeogenic and Glycogenolytic States Using Hyperpolarized

Glycogenolysis and gluconeogenesis are sensitive to nutritional state, and the net direction of flux is controlled by multiple enzymatic steps. This delicate balance in the liver is disrupted by a variety of pathological states including cancer and diabetes mellitus. Hyperpolarized carbon-13 magnetic resonance is a new metabolic imaging technique that can probe intermediary metabolism nondestructively. There are currently no methods to rapidly distinguish livers in a gluconeogenic from glycogenolytic state. Here we use the gluconeogenic precursor dihydroxyacetone (DHA) to deliver hyperpolarized carbon-13 to the perfused mouse liver. DHA enters gluconeogenesis at the level of the trioses. Perfusion conditions were designed to establish either a gluconeogenic or a glycogenolytic state. Unexpectedly, we found that [2- 13 C]DHA was metabolized within a few seconds to the common intermediates and end products of both glycolysis and gluconeogenesis under both conditions, including [2,5- 13 C]glucose, [2- 13 C]glycerol 3-phosphate, [2- 13 C]phosphoenolpyruvate (PEP), [2- 13 C]pyruvate, [2- 13 C]alanine, and [2- 13 C]lactate. [2- 13 C]Phosphoenolpyruvate, a key branch point