Heptanoate as a neural fuel

Energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain

Isaac Marin-Valencia, Levi B. Good, Qian Ma, Craig R. Malloy, Juan M. Pascual

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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 [5,6,7-13C3 ]heptanoate was examined in the normal mouse brain and in G1D by 13C-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 13C, 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 13C 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.

Original languageEnglish (US)
Pages (from-to)175-182
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume33
Issue number2
DOIs
StatePublished - Feb 2013

Fingerprint

Heptanoates
Facilitative Glucose Transport Proteins
Acetyl Coenzyme A
Neurotransmitter Agents
Brain
Glucose
Glutamine
Seizures
Ketogenic Diet
Citric Acid Cycle
Gluconeogenesis
Ketones
Pyruvic Acid
Neuroglia
Liquid Chromatography
Anticonvulsants
Gas Chromatography-Mass Spectrometry
Energy Metabolism
Glutamic Acid
Mass Spectrometry

Keywords

  • glucose
  • glutamine
  • nuclear magnetic resonance
  • transporter

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

Heptanoate as a neural fuel : Energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain. / Marin-Valencia, Isaac; Good, Levi B.; Ma, Qian; Malloy, Craig R.; Pascual, Juan M.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 33, No. 2, 02.2013, p. 175-182.

Research output: Contribution to journalArticle

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