Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function

Kah Ni Tan, Catalina Carrasco-Pozo, Tanya S. McDonald, Michelle Puchowicz, Karin Borges

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The hypothesis that chronic feeding of the triglycerides of octanoate (trioctanoin) and decanoate (tridecanoin) in “a regular non-ketogenic diet” is anticonvulsant was tested and possible mechanisms of actions were subsequently investigated. Chronic feeding of 35E% of calories from tridecanoin, but not trioctanoin, was reproducibly anticonvulsant in two acute CD1 mouse seizure models. The levels of beta-hydroxybutyrate in plasma and brain were not significantly increased by either treatment relative to control diet. The respective decanoate and octanoate levels are 76 µM and 33 µM in plasma and 1.17 and 2.88 nmol/g in brain. Tridecanoin treatment did not alter the maximal activities of several glycolytic enzymes, suggesting that there is no reduction in glycolysis contributing to anticonvulsant effects. In cultured astrocytes, 200 µM of octanoic and decanoic acids increased basal respiration and ATP turnover, suggesting that both medium chain fatty acids are used as fuel. Only decanoic acid increased mitochondrial proton leak which may reduce oxidative stress. In mitochondria isolated from hippocampal formations, tridecanoin increased respiration linked to ATP synthesis, indicating that mitochondrial metabolic functions are improved. In addition, tridecanoin increased the plasma antioxidant capacity and hippocampal mRNA levels of heme oxygenase 1, and FoxO1.

Original languageEnglish (US)
Pages (from-to)2035-2048
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number6
DOIs
StatePublished - Jun 1 2017

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Anticonvulsants
Antioxidants
Decanoates
Decanoic Acids
Respiration
Caprylates
Adenosine Triphosphate
Diet
Heme Oxygenase-1
3-Hydroxybutyric Acid
Brain
Glycolysis
Astrocytes
Protons
Hippocampus
Mitochondria
Seizures
Triglycerides
Oxidative Stress
Fatty Acids

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function. / Tan, Kah Ni; Carrasco-Pozo, Catalina; McDonald, Tanya S.; Puchowicz, Michelle; Borges, Karin.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 37, No. 6, 01.06.2017, p. 2035-2048.

Research output: Contribution to journalArticle

Tan, Kah Ni ; Carrasco-Pozo, Catalina ; McDonald, Tanya S. ; Puchowicz, Michelle ; Borges, Karin. / Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function. In: Journal of Cerebral Blood Flow and Metabolism. 2017 ; Vol. 37, No. 6. pp. 2035-2048.
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