Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function

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.

Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium‐chain triglyceride ketogenic diet

“…These findings, coupled with the direct inhibitory effect of C10 on AMPA receptors 6 , provide mechanistic evidence whereby C10 could elicit seizure control. The anti-seizure properties of C10 are further supported by observations, in vivo, that report that mice fed with a C10-enriched chow display significantly improved seizure tolerance and brain antioxidant capacity [7][8][9][10][11] . In studies conducted by Wlaź et al, C10 levels were also determined in the brains of mice following C10-enriched feeding.…”

Sulforaphane Protects against High Cholesterol‐Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic β‐Cells Function

“…This assay allows the study of the contribution and function of complexes I, II, and IV in the ETC in terms of OCR. Mitochondria were isolated as previously described [6, 7, 21]. Briefly, cells were harvested, washed in a Ca 2+ /Mg 2+ -free PBS, and centrifuged (10 min; 1,000 g ; 4°C).…”

New insights into the mechanisms of the ketogenic diet

“…Branched octanoic acid compounds have been generated that show promising antiseizure activity in in vitro and in vivo seizure models, without affecting histone deacetylase activity [21]. Chronic feeding of diet with 35% of the calories derived from tridecanoin but not from trioctanoin was anticonvulsant in two mouse models in the absence of increased plasma and brain BHB [22 • ]. Only tridecanoin but not trioctanoin improved mitochondrial metabolic functions and antioxidant capacity [22].…”

“…Chronic feeding of diet with 35% of the calories derived from tridecanoin but not from trioctanoin was anticonvulsant in two mouse models in the absence of increased plasma and brain BHB [22 • ]. Only tridecanoin but not trioctanoin improved mitochondrial metabolic functions and antioxidant capacity [22]. Specifically, decanoic acid but not octanoic acid improved mitochondrial biogenesis as well as mitochondrial numbers through a PPARγ-mediated mechanism in neuronal cell culture systems [23,24]; decanoic acid led to an increase in the transcription of genes related to fatty acid metabolism, while downregulating genes involved in glucose metabolism [23].…”