TY  - JOUR
A1  - Koch, Konrad
A1  - Berressem, Dirk
A1  - Konietzka, Jan
A1  - Thinnes, Anna
A1  - Eckert, Gunter P.
A1  - Klein, Jochen
T1  - Hepatic ketogenesis induced by middle cerebral artery occlusion in mice
T2  - Journal of the American Heart Association
N2  - 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.
KW  - cerebral ischemia
KW  - citrate
KW  - glucose
KW  - ketone bodies
KW  - lactate
KW  - middle cerebral artery occlusion
KW  - mouse
KW  - succinate
KW  - β‐hydroxybutyrate
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45791
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-457914
VL  - 6
IS  - (4): e005556
SP  - 1
EP  - 9
ER  -