title: Metabolic products of [2-(13) C]ethanol in the rat brain after chronic ethanol exposure.
abstract: Most ingested ethanol is metabolized in the liver to acetaldehyde and then to acetate, which can be oxidized by the brain. This project assessed whether chronic exposure to alcohol can increase cerebral oxidation of acetate. Through metabolism, acetate may contribute to long-term adaptation to drinking. Two groups of adult male Sprague-Dawley rats were studied, one treated with ethanol vapor and the other given room air. After 3 weeks the rats received an intravenous infusion of [2-(13) C]ethanol via a lateral tail vein for 2 h. As the liver converts ethanol to [2-(13) C]acetate, some of the acetate enters the brain. Through oxidation the (13) C is incorporated into the metabolic intermediate α-ketoglutarate, which is converted to glutamate (Glu), glutamine (Gln), and GABA. These were observed by magnetic resonance spectroscopy and found to be (13) C-labeled primarily through the consumption of ethanol-derived acetate. Brain Gln, Glu, and, GABA (13) C enrichments, normalized to (13) C-acetate enrichments in the plasma, were higher in the chronically treated rats than in the ethanol-naïve rats, suggesting increased cerebral uptake and oxidation of circulating acetate. Chronic ethanol exposure increased incorporation of systemically derived acetate into brain Gln, Glu, and GABA, key neurochemicals linked to brain energy metabolism and neurotransmission. The liver converts ethanol to acetate, which may contribute to long-term adaptation to drinking. Astroglia oxidize acetate and generate neurochemicals, while neurons and glia may also oxidize ethanol. When (13) C-ethanol is administered intravenously, (13) C-glutamine, glutamate, and GABA, normalized to (13) C-acetate, were higher in chronic ethanol-exposed rats than in control rats, suggesting that ethanol exposure increases cerebral oxidation of circulating acetate.
authors.affiliation: State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Science, Wuhan, Hubei, China; Department of Diagnostic Radiology, School of Medicine, Yale University, New Haven, Connecticut, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Hongying
authors.initials: H
authors.lastname: Du
authors.forename: Xiaoxian
authors.initials: X
authors.lastname: Ma
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.forename: Laura
authors.initials: L
authors.lastname: Castracane
authors.forename: Ting-Kai
authors.initials: TK
authors.lastname: Li
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Behar
authors.forename: Graeme F
authors.initials: GF
authors.lastname: Mason
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000085:Acetates / Q000378:metabolism; D000280:Administration, Inhalation; D000818:Animals; D001711:Biotransformation; D001923:Brain Chemistry / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002149:Energy Intake; D000431:Ethanol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008872:Microwaves; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016707:Tissue Fixation
chemical_list: D000085:Acetates; D002492:Central Nervous System Depressants; D019344:Lactic Acid; D000431:Ethanol; D005947:Glucose; D020155:3-Hydroxybutyric Acid
keywords: NMR; acetate; brain metabolism; ethanol; rats
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