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Abstract #1028

1H-[13C] MRS Ex Vivo Study of Cortical Ketone Body Utilization in Awake Rats During Fasting-Induced Ketosis

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.