Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain

Hsieh, Ya-Ju; Wu, Liang; Ke, Chien-Chih; Chang, Chi Wei; Kuo, Jung Wen; Huang, Wen Sheng; Chen, Fu Du; Yang, Bohan; Tai, Hsiao Ting; Chen, Sharon Chia-Ju; Liu, Ru‐Shi

doi:10.1111/acer.13573

Cited by 4 publications

(2 citation statements)

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“…These cellular adaptations may contribute to tolerance and dependence. Animal and human studies confirm that chronic alcohol consumption is associated with greater brain acetate uptake and utilization (Hsieh et al, 2018; Jiang et al, 2013; Volkow et al, 2013). In heavy drinkers, cessation of drinking is associated with development of withdrawal symptoms.…”

Section: Introductionmentioning

confidence: 93%

“…In longstanding, chronic EtOH consumption, as in AUDs, the capacity for EtOH and acetate metabolism increases over time, effectively "priming" cells to use these substrates instead of glucose for energy (Enculescu et al, 2019;Hsieh et al, 2018;Wilson & Matschinsky, 2020). Compared to drinkers without harmful alcohol use, heavy drinkers have higher systemic acetate (Nuutinen et al, 1985) and more rapid turnover of acetate in the brain (Jiang et al, 2013).…”

Section: Alcohol Acetate and Brain Energymentioning

confidence: 99%

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Effects of acetate on cerebral blood flow, systemic inflammation, and behavior in alcohol use disorder

Tanabe

Neff

Sutton

et al. 2021

Alcoholism Clin & Exp Res

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Background Alcohol use disorders (AUDs) are associated with altered regulation of physiological processes in the brain. Acetate, a metabolite of ethanol, has been implicated in several processes that are disrupted in AUDs including transcriptional regulation, metabolism, inflammation, and neurotransmission. To further understand the effects of acetate on brain function in AUDs, we investigated the effects of acetate on cerebral blood flow (CBF), systemic inflammatory cytokines, and behavior in AUD. Methods Sixteen participants with AUD were recruited from a nonmedical, clinically managed detoxification center. Each participant received acetate and placebo in a randomly assigned order of infusion and underwent 3T MR scanning using quantitative pseudo‐continuous arterial spin labeling. Participants and the study team were blinded to the infusion. CBF values (ml/100 g/min) extracted from thalamus were compared between placebo and acetate using a mixed effect linear regression model accounting for infusion order. Voxel‐wise CBF comparisons were set at threshold of p < 0.05 cluster‐corrected for multiple comparisons, voxel‐level p < 0.0001. Plasma cytokine levels and behavior were also assessed between infusions. Results Fifteen men and 1 woman were enrolled with Alcohol Use Disorders Identification Test (AUDIT) scores between 13 and 38 with a mean of 28.3 ± 9.1. Compared to placebo, acetate administration increased CBF in the thalamus bilaterally (Left: 51.2 vs. 68.8, p < 0.001; Right: 53.7 vs. 69.6, p = 0.001), as well as the cerebellum, brainstem, and cortex. Older age and higher AUDIT scores were associated with increases in acetate‐induced thalamic blood flow. Cytokine levels and behavioral measures did not differ between placebo and acetate infusions. Conclusions This pilot study in AUD suggests that during the first week of abstinence from alcohol, the brain's response to acetate differs by brain region and this response may be associated with the severity of alcohol dependence.

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Section: Introductionmentioning

confidence: 93%

Section: Alcohol Acetate and Brain Energymentioning

confidence: 99%

Effects of acetate on cerebral blood flow, systemic inflammation, and behavior in alcohol use disorder

Tanabe

Neff

Sutton

et al. 2021

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

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Excipient toxicity and safety

Pandey¹,

Polaka²,

Nalla³

et al. 2022

Pharmacokinetics and Toxicokinetic Considerations

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Effects of Alcohol and Acetate on Cerebral Blood Flow: A Pilot Study

Tanabe

Yamamoto

Sutton

et al. 2019

Alcoholism Clin & Exp Res

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BackgroundAcute alcohol produces effects on cerebral metabolism and blood flow. Alcohol is converted to acetate, which serves as a source of energy for the brain and is an agonist at G protein‐coupled receptors distributed in different cell types in the body including neurons. Acetate has been hypothesized to play a role in the cerebral blood flow (CBF) response after alcohol ingestion. We tested whether administration of acetate would alter CBF in a pattern similar to or different from that of alcohol ingestion in healthy individuals.MethodsTwenty‐four healthy participants were assigned by convenience to receive either 0.6 g/kg alcohol orally (n = 12) or acetate intravenously (n = 12). For each participant, CBF maps were acquired using an arterial spin labeling sequence on a 3T magnetic resonance scanner after placebo and after drug administration. Whole‐brain CBF maps were compared between placebo and drug using a paired t‐test, and set at a threshold of p < 0.05 corrected for multiple comparisons (k ≥ 142 voxels, ≥3.78 cm3), voxel‐level p < 0.005. Intoxication was measured after placebo and drug administration with a Subjective High Assessment Scale (SHAS‐7).ResultsCompared to placebo, alcohol and acetate were associated with increased CBF in the medial thalamus. Alcohol, but not acetate, was associated with increased CBF in the right orbitofrontal, medial prefrontal and cingulate cortex, and hippocampus. Plasma acetate levels increased following administration of alcohol and acetate and did not differ between the 2 arms. Alcohol, but not acetate, was associated with an increase in SHAS‐7 scores (p < 0.001).ConclusionsIncreased thalamic CBF associated with either alcohol or acetate administration suggests that the thalamic CBF response after alcohol could be mediated by acetate. Compared to other brain regions, thalamus may differ in its ability to metabolize acetate or expression of receptors responsive to acetate. Increased prefrontal and limbic CBF associated with alcohol may be linked to alcohol's behavioral effects.

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Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain

Cited by 4 publications

References 36 publications

Effects of acetate on cerebral blood flow, systemic inflammation, and behavior in alcohol use disorder

Effects of acetate on cerebral blood flow, systemic inflammation, and behavior in alcohol use disorder

Excipient toxicity and safety

Effects of Alcohol and Acetate on Cerebral Blood Flow: A Pilot Study

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