title: Hepatic Ketogenesis Induced by Middle Cerebral Artery Occlusion in Mice.
abstract: BACKGROUND
  Ketone 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.
  
  
  RESULTS
  Mice 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Department of Pharmacology, FB 14, Goethe University, Frankfurt, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Koch
authors.affiliation: Department of Pharmacology, FB 14, Goethe University, Frankfurt, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Berressem
authors.affiliation: Department of Pharmacology, FB 14, Goethe University, Frankfurt, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Konietzka
authors.affiliation: Department of Pharmacology, FB 14, Goethe University, Frankfurt, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Thinnes
authors.affiliation: Department of Pharmacology, FB 14, Goethe University, Frankfurt, Germany.
authors.forename: Gunter P
authors.initials: GP
authors.lastname: Eckert
authors.affiliation: Department of Pharmacology, FB 14, Goethe University, Frankfurt, Germany klein@em.uni-frankfurt.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Klein
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism; D019343:Citric Acid / Q000378:metabolism; D000070601:Diet, Carbohydrate Loading; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D007657:Ketone Bodies / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D017551:Microdialysis; D011433:Propranolol / Q000494:pharmacology; D013024:Soybean Oil; D019802:Succinic Acid / Q000378:metabolism; D014280:Triglycerides
chemical_list: D000319:Adrenergic beta-Antagonists; D007657:Ketone Bodies; D014280:Triglycerides; D019343:Citric Acid; C531010:triheptanoin; D013024:Soybean Oil; D011433:Propranolol; D019802:Succinic Acid; D005947:Glucose; D020155:3-Hydroxybutyric Acid
keywords: cerebral ischemia; citrate; glucose; ketone bodies; lactate; middle cerebral artery occlusion; mouse; succinate; β‐hydroxybutyrate