Rationale:
The ketogenic diet (KD) has been shown to effectively reduce seizures in patients. Research indicates that ketogenic medium-chain triglycerides (MCTs) enhance brain energy metabolism in adults with brain disorders. However, it is uncertain whether MCTs are altered in peripheral metabolites in children with epilepsy. The role and mechanism of MCTs in pediatric epilepsy are still not well understood.
Methods:
We utilized LC-MS untargeted metabolomics to analyze blood metabolites in children with epilepsy. Among the significantly altered metabolites, octanoic acid (OA), a key component of medium-chain triglycerides (MCTs), was notably elevated, while decanoic acid showed no significant changes. To investigate the role of MCTs in pediatric seizures, we used the PTZ epilepsy model to evaluate the effects of OA on seizure activity through behavioral assessments, Nissl staining, and immunofluorescence staining in the brain.
Results:
Of the 518 metabolites analyzed in plasma samples, the top 20 were identified, with 14 showing increased levels and 6 showing decreased levels. In the PTZ-induced epilepsy model, octanoic acid (OA) significantly extended seizure latency but did not affect seizure grade or duration. Mechanistically, OA enhanced GPR40 activation and reduced astrocyte activation in the hippocampus.
Conclusions:
In this study, metabolites in the peripheral blood of epileptic children were identified and validated, with octanoic acid (OA) potentially playing a protective role, as confirmed by subsequent animal experiments. OA enhanced nervous system protection through GPR40 activation. These findings suggest that monitoring OA levels may aid in the early diagnosis and treatment of pediatric epilepsy.
Funding: National Nature Science Foundtion of China, 82171452