Reversible alterations of brain acetate metabolism associated with alcohol consumption

Abstract Alcohol consumption elevates circulating acetate. Prior studies showed that acute alcohol reduces brain glucose uptake and increases brain acetate oxidation. Previously we showed that heavy drinkers have elevated capacity to oxidize brain acetate. Here we repeat the study, adding individuals with alcohol use disorder (AUD). Four groups were enrolled. The analysis data set included Light Drinkers (LD, n = 13, female = 5), at-risk Heavy Drinkers (HD, n = 15, female = 7), AUD patients in long-term recovery (≥6 months; AUD LTR , n = 6, female = 1), and a separate group of AUD treatment-seekers (AUD Tx , n = 12, female = 1) underwent medically supervised detoxification, scanned at ~1 week abstinence ( n = 9) and 1 month ( n = 10). Seven AUD Tx participants successfully completed scans at both time points. We infused participants with [2- 13 C]acetate during magnetic resonance spectroscopy (MRS) of 13 C-glutamate (Glu) and 13 C-glutamine (Gln) in the brain, to measure the cerebral metabolic rate for acetate (CMR Ac ) and the neuronal tricarboxylic acid cycle relative to glutamate-glutamine neurotransmitter cycling (V tcaN /V cycle ; Energy Per Cycle: EPC). There was a group effect for CMR Ac ( p = 0.007) primarily owing to lower CMR Ac in AUD Tx at 1 week. Furthermore, higher CMR Ac was observed among HD compared to LD participants, as previously reported. CMR Ac was similar between the AUD LTR and HD groups. In a separate within-subject comparison among AUD Tx participants, CMR Ac increased after 1 month to levels similar to those of LD. EPC was similar among the groups, representing normal glutamate-glutamine cycling versus energetics. In summary, abstinence reversed the lower acetate oxidation in early AUD, showing that just a few weeks of recovery can normalize this metabolic abnormality.