Hepatic ketogenesis induced by middle cerebral artery occlusion in mice

Autor: Jan Konietzka, Konrad Koch, Jochen Klein, Anna Thinnes, Dirk Berressem, Gunter P. Eckert
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
middle cerebral artery occlusion
Microdialysis
Succinic Acid
Ketone Bodies
cerebral ischemia
Brain Ischemia
Mice
0302 clinical medicine
Ischemia
Ketogenesis
citrate
Middle cerebral artery occlusion
glucose
Original Research
3-Hydroxybutyric Acid
Brain
Infarction
Middle Cerebral Artery
Propranolol
Stroke
Liver
Ketone bodies
Female
Diet
Carbohydrate Loading
Cardiology and Cardiovascular Medicine
medicine.medical_specialty
Adrenergic beta-Antagonists
Diet
High-Fat
Neuroprotection
Citric Acid
Gas Chromatography-Mass Spectrometry
β‐hydroxybutyrate
03 medical and health sciences
Internal medicine
medicine
Animals
ddc:610
Triglycerides
mouse
Ischemic Stroke
lactate
business.industry
succinate
Soybean Oil
Disease Models
Animal
Metabolism
030104 developmental biology
Endocrinology
Cerebrovascular Disease/Stroke
business
030217 neurology & neurosurgery
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Popis: 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. Methods and 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.
Databáze: OpenAIRE
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