The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells

@article{Hughes2014TheKD,
  title={The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells},
  author={Sean David Hughes and Marta Kanabus and Glenn W. Anderson and Iain P. Hargreaves and Tricia Rutherford and Maura O’ Donnell and J. Helen Cross and Shamima Rahman and Simon Eaton and Simon J R Heales},
  journal={Journal of Neurochemistry},
  year={2014},
  volume={129},
  pages={426 - 433}
}
The Ketogenic diet (KD) is an effective treatment with regards to treating pharmaco‐resistant epilepsy. However, there are difficulties around compliance and tolerability. Consequently, there is a need for refined/simpler formulations that could replicate the efficacy of the KD. One of the proposed hypotheses is that the KD increases cellular mitochondrial content which results in elevation of the seizure threshold. Here, we have focussed on the medium‐chain triglyceride form of the diet and… Expand
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References

SHOWING 1-10 OF 43 REFERENCES
Seizure control by ketogenic diet-associated medium chain fatty acids
TLDR
Specific medium chain fatty acids are identified that provide significantly enhanced in vitro seizure control compared to VPA and a related new family of compounds that are more potent than VPA in seizure control with a reduced potential for side effects are highlighted. Expand
Effect of Peroxynitrite on the Mitochondrial Respiratory Chain: Differential Susceptibility of Neurones and Astrocytes in Primary Culture
TLDR
It is concluded that the acute exposure of ONOO− selectively damages neurones, whereas astrocytes remain unaffected, and intracellular glutathione appears to be an important factor for ameliorating ONOO‐‐mediated mitochondrial damage. Expand
Ketogenic Diet Increases Glutathione Peroxidase Activity in Rat Hippocampus
TLDR
It is suggested that the higher activity of this enzyme induced by ketogenic diet in hippocampus might contribute to protect this structure from neurodegenerative sequelae of convulsive disorders. Expand
Mitochondrial activity in Pompe's disease.
TLDR
Observations demonstrate that caution should be exercised when analyzing and interpreting data obtained from tissue homogenates in general and in those prepared from tissues in which the wet weight of tissue may be altered, for example, by pathologic accumulation of carbohydrate or lipid. Expand
Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity
TLDR
It is shown that suppression of ROS diminishes pro-opiomelanocortin (POMC) cell activation and promotes the activity of neuropeptide Y and agouti-related peptide-co-producing neurons and feeding, whereas ROS-activates POMC neurons and reduces feeding. Expand
PPARγ stimulation promotes mitochondrial biogenesis and prevents glucose deprivation-induced neuronal cell loss
TLDR
The data indicate that a prolonged PPARgamma stimulation, by repeated administration of nanomolar pioglitazone or rosiglitaz one concentrations, decreases GD-induced loss of differentiated SH-SY5Y cells, and suggest that mitochondrial biogenesis may contribute to these effects. Expand
Ketogenic diet. Update and application.
TLDR
The division of Pediatric Neurology at King Faisal Specialist Hospital & Research Center in Jeddah is one of very few centers that provide this treatment option in the Middle East, and it is critical that this treatment is provided to highly selected children with committed parents. Expand
Identification and Mechanism of 10-Carbon Fatty Acid as Modulating Ligand of Peroxisome Proliferator-activated Receptors*
TLDR
Decanoic acid, a 10-carbon fatty acid and a major component of medium chain triglyceride oils, is a direct ligand of PPARγ, suggesting that DA is a modulating ligand for PPARs, and the structure can aid in designing better and safer PParγ-based drugs. Expand
Ketonemia and Seizures: Metabolic and Anticonvulsant Effects of Two Ketogenic Diets in Childhood Epilepsy
TLDR
The data suggest that one or both of these compounds either have direct anticonvulsant effects or produce rapidly reversible changes in cerebral metabolism, which in turn affect cerebral excitability. Expand
Energy Thresholds in Brain Mitochondria
TLDR
Results suggest that, in mitochondria of synaptic origin, complex I activity has a major control of oxidative phosphorylation, such that when a threshold of 25% inhibition is exceeded, energy metabolism is severely impaired, resulting in a reduced synthesis of ATP. Expand
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