Increased brain uptake and oxidation of acetate in heavy drinkers
Lihong Jiang, Barbara Irene Gulanski, Henk M. De Feyter, Stuart A. Weinzimer, Brian Pittman, Elizabeth Guidone, Julia Koretski, Susan Harman, Ismene L. Petrakis, John H. Krystal, Graeme F. Mason
Lihong Jiang, Barbara Irene Gulanski, Henk M. De Feyter, Stuart A. Weinzimer, Brian Pittman, Elizabeth Guidone, Julia Koretski, Susan Harman, Ismene L. Petrakis, John H. Krystal, Graeme F. Mason
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Research Article Metabolism

Increased brain uptake and oxidation of acetate in heavy drinkers

Abstract

When a person consumes ethanol, the body quickly begins to convert it to acetic acid, which circulates in the blood and can serve as a source of energy for the brain and other organs. This study used 13C magnetic resonance spectroscopy to test whether chronic heavy drinking is associated with greater brain uptake and oxidation of acetic acid, providing a potential metabolic reward or adenosinergic effect as a consequence of drinking. Seven heavy drinkers, who regularly consumed at least 8 drinks per week and at least 4 drinks per day at least once per week, and 7 light drinkers, who consumed fewer than 2 drinks per week were recruited. The subjects were administered [2-13C]acetate for 2 hours and scanned throughout that time with magnetic resonance spectroscopy of the brain to observe natural 13C abundance of N-acetylaspartate (NAA) and the appearance of 13C-labeled glutamate, glutamine, and acetate. Heavy drinkers had approximately 2-fold more brain acetate relative to blood and twice as much labeled glutamate and glutamine. The results show that acetate transport and oxidation are faster in heavy drinkers compared with that in light drinkers. Our finding suggests that a new therapeutic approach to supply acetate during alcohol detoxification may be beneficial.

Authors

Lihong Jiang, Barbara Irene Gulanski, Henk M. De Feyter, Stuart A. Weinzimer, Brian Pittman, Elizabeth Guidone, Julia Koretski, Susan Harman, Ismene L. Petrakis, John H. Krystal, Graeme F. Mason

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Figure 4

Metabolic pathways showing brain uptake of [2-13C]acetate and transfer of the 13C labeling to glutamine and glutamate in astroglia and neurons.

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Metabolic pathways showing brain uptake of [2-13C]acetate and transfer o...
Astroglia consume acetate, while neurons and astroglia both consume glucose (Glc). The acetate labeled at the methyl group, whose carbon is designated 2 (Ac2), enters the astroglia and the TCA cycle to form C2-labeled acetyl CoA (Ac2CoA). In the first turn of the Krebs cycle, it labels the C4 of astroglial α-ketoglutarate (α-KGA4), which exchanges to form glutamate C4 (GluA4). Astroglia convert glutamate to glutamine, forming glutamine C4 (Gln4), which is transferred to neurons, converted, and mixed with the large neuronal pool of glutamate (GluN4). Some of the glutamate is released as part of glutamate-glutamine cycling, and some exchanges to form neuronal α-ketoglutarate (α-KGN4). In both compartments, the carbon continues through the cycle and labels oxaloacetate (OAA) and labels glutamate and glutamine at C3 (data not shown) but does not return to the C4 of glutamate and glutamine. Meanwhile, the vast majority of glucose remains unlabeled and dilutes the pool of acetyl CoA and the Krebs cycle intermediates in neurons and astroglia. AcCoA, acetyl-CoA; Lac, lactate; Pyr, pyruvate.