1. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Science, , Wuhan, Hubei, China;2. Department of Diagnostic Radiology, School of Medicine, Yale University, , New Haven, Connecticut, USA;3. College of Food Science and Technology and the MOE Key Laboratory of Environment Correlative Dietology, Huazhong Agricultural University, , Wuhan, China;4. Department of Psychiatry, School of Medicine, Yale University, , New Haven, Connecticut, USA;5. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, , Durham, NC, USA
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 2‐13C]ethanol via a lateral tail vein for 2 h. As the liver converts ethanol to 2‐13C]acetate, some of the acetate enters the brain. Through oxidation the 13C 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 13C‐labeled primarily through the consumption of ethanol‐derived acetate. Brain Gln, Glu, and, GABA 13C enrichments, normalized to 13C‐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.
