title: Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides.
abstract: Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of β-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6 Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain.
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Tanya S
authors.initials: TS
authors.lastname: McDonald
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Kah Ni
authors.initials: KN
authors.lastname: Tan
authors.affiliation: Metabolomics Australia, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Hodson
authors.affiliation: Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Karin
authors.initials: K
authors.lastname: Borges
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000737:chemistry; D002210:Caprylates / Q000008:administration & dosage* / Q000737:chemistry; D002952:Citric Acid Cycle / Q000187:drug effects; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012640:Seizures / Q000178:diet therapy / Q000378:metabolism / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000927:Anticonvulsants; D002210:Caprylates; D014280:Triglycerides; C531010:triheptanoin; C003637:tricaprylin; D005947:Glucose