Golam M.I. Chowdhury1, Robin A. de Graaf1, Lihong Jiang1, Graeme F. Mason1, Douglas L. Rothman1, Kevin L. Behar2
1Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA; 2Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA
In this study we measured the rates of utilization of 3-hydroxybutyrate (3-HB) and glucose metabolism in awake, unrestrained rats, fasted for 36h so as to induce a significant level of ketosis and infused with either [2,4- sup>13</sup>C]-3-HB or [2- sup>13</sup>C]acetate for different periods of time followed by rapid euthanasia. sup>13</sup>C labeled glutamate and glutamine were measured ex vivo in cortical extracts and a two-compartment (neuron-astroglia) metabolic model was fitted to the time course data to extract metabolic flux information. Under awake conditions 3-HB utilization in the ketotic animals comprised 37% of total tricarboxylic acid cycle flux in neurons. A high rate of glutamine synthesis was seen under the ketotic conditions suggesting that anaplerosis was increased.