title: Acute alcohol intoxication decreases glucose metabolism but increases acetate uptake in the human brain.
abstract: Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also the metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FDG) with the largest decrements in cerebellum and occipital cortex and the smallest in the thalamus. In contrast, alcohol intoxication caused a significant increase in [1-(11)C]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in the cerebellum and the smallest in the thalamus. In heavy alcohol drinkers [1-(11)C]acetate brain uptake during alcohol challenge tended to be higher than in occasional drinkers (p<0.06) and the increases in [1-(11)C]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-(11)C]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (i.e. ketogenic diets) may have in alcoholics undergoing alcohol detoxification.
authors.affiliation: National Institute on Drug Abuse, Bethesda, MD 20892, USA. nvolkow@nida.nih.gov
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Alexoff
authors.forename: Jean
authors.initials: J
authors.lastname: Logan
authors.forename: Lisa
authors.initials: L
authors.lastname: Muench
authors.forename: Colleen
authors.initials: C
authors.lastname: Shea
authors.forename: Frank
authors.initials: F
authors.lastname: Telang
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.forename: Christopher
authors.initials: C
authors.lastname: Wong
authors.forename: Helene
authors.initials: H
authors.lastname: Benveniste
authors.forename: Dardo
authors.initials: D
authors.lastname: Tomasi
mesh_terms: D000085:Acetates / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D000435:Alcoholic Intoxication / Q000209:etiology* / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002244:Carbon / Q000493:pharmacokinetics*; D002648:Child; D000431:Ethanol / Q000506:poisoning*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D000085:Acetates; D019275:Radiopharmaceuticals; C438206:carbon-11 acetate; D019788:Fluorodeoxyglucose F18; D000431:Ethanol; D002244:Carbon; D005947:Glucose