Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 33, Issue 2, Pages 175-182Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2012.151
Keywords
glucose; glutamine; nuclear magnetic resonance; transporter
Categories
Funding
- NIDDK [1U24DK076174]
- Fundacion Caja Madrid
- NIH [NS077015, RR002584, EB000461, F32NS065640]
- Dallas Women's Foundation (Billingsley Fund)
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It has been postulated that triheptanoin can ameliorate seizures by supplying the tricarboxylic acid cycle with both acetyl-CoA for energy production and propionyl-CoA to replenish cycle intermediates. These potential effects may also be important in other disorders associated with impaired glucose metabolism because glucose supplies, in addition to acetyl-CoA, pyruvate, which fulfills biosynthetic demands via carboxylation. In patients with glucose transporter type I deficiency (G1D), ketogenic diet fat (a source only of acetyl-CoA) reduces seizures, but other symptoms persist, providing the motivation for studying heptanoate metabolism. In this work, metabolism of infused [5,6,7-C-13(3)]heptanoate was examined in the normal mouse brain and in G1D by C-13-nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). In both groups, plasma glucose was enriched in C-13, confirming gluconeogenesis from heptanoate. Acetyl-CoA and glutamine levels became significantly higher in the brain of G1D mice relative to normal mice. In addition, brain glutamine concentration and C-13 enrichment were also greater when compared with glutamate in both animal groups, suggesting that heptanoate and/or C5 ketones are primarily metabolized by glia. These results enlighten the mechanism of heptanoate metabolism in the normal and glucose-deficient brain and encourage further studies to elucidate its potential antiepileptic effects in disorders of energy metabolism. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 175-182; doi:10.1038/jcbfm.2012.151; published online 17 October 2012
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