BackgroundKetone bodies are known to substitute for glucose as brain fuel when glucose availability is low. Ketogenic diets have been described as neuroprotective. Similar data have been reported for triheptanoin, a fatty oil and anaplerotic compound. In this study, we monitored the changes of energy metabolites in liver, blood, and brain after transient brain ischemia to test for ketone body formation induced by experimental stroke.Methods and ResultsMice were fed a standard carbohydrate‐rich diet or 2 fat‐rich diets, 1 enriched in triheptanoin and 1 in soybean oil. Stroke was induced in mice by middle cerebral artery occlusion for 90 minutes, followed by reperfusion. Mice were sacrificed, and blood plasma and liver and brain homogenates were obtained. In 1 experiment, microdialysis was performed. Metabolites (eg glucose, β‐hydroxybutyrate, citrate, succinate) were determined by gas chromatography–mass spectrometry. After 90 minutes of brain ischemia, β‐hydroxybutyrate levels were dramatically increased in liver, blood, and brain microdialysate and brain homogenate, but only in mice fed fat‐rich diets. Glucose levels were changed in the opposite manner in blood and brain. Reperfusion decreased β‐hydroxybutyrate and increased glucose within 60 minutes. Stroke‐induced ketogenesis was blocked by propranolol, a β‐receptor antagonist. Citrate and succinate were moderately increased by fat‐rich diets and unchanged after stroke.ConclusionsWe conclude that brain ischemia induces the formation of β‐hydroxybutyrate (ketogenesis) in the liver and the consumption of β‐hydroxybutyrate in the brain. This effect seems to be mediated by β‐adrenergic receptors.
Using microdialysis in C57Bl6 mice, we monitored cholinergic activity in the hypothalamus. Food intake after an overnight fast caused a 3-fold increase of extracellular acetylcholine (ACh) concentrations in the hypothalamus. The effect lasted for about 30 min. Food containing no calories (kaolin pellets), or food that was presented but not accessible, also increased ACh release. In contrast, injections of glucose or β-hydroxybutyrate did not change extracellular ACh. Mice deficient in muscarinic M receptors had the same cholinergic response as wild-type mice. We conclude that the increase of ACh in the hypothalamus was not caused by local detection of nutrients but by anticipation of food intake. This suggests the involvement of motivational circuits in the basal forebrain which is reinforced by the fact that we found slight increases of ACh in the nucleus accumbens during feeding.
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