Increased brain uptake and oxidation of acetate in heavy drinkers
Lihong Jiang, … , John H. Krystal, Graeme F. Mason
Lihong Jiang, … , John H. Krystal, Graeme F. Mason
Published March 8, 2013
Citation Information: J Clin Invest. 2013;123(4):1605-1614. https://doi.org/10.1172/JCI65153.
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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 5

Metabolic rates calculated based on individual 13C time courses of Glu4 and Gln4 and the steady state of Glu3 and Gln3.

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Metabolic rates calculated based on individual 13C time courses of Glu4 ...
The value of VxA, which is the rate of exchange between astroglial α-ketoglutarate and glutamate, has not been determined. The kinetics was therefore tested over a range of values of VxA. Its minimum possible value is equal to the rate of the TCA cycle VtcaA, and, for values above 10×VtcaA, there is negligible difference in the kinetic impact compared with infinity (70), so VxA = 10×VtcaA was selected as the maximum of the range. (A) CMRac was calculated assuming VxA= 10×VtcaA. CMRac was significantly greater in the heavy drinking group (P = 0.02). (B) Astroglial TCA cycle (VtcaA) rates did not differ (P = 0.58) when VxA= 10×VtcaA. (C) CMRac was calculated assuming VxA = VtcaA, showing significant differences between heavy drinkers and light drinkers (P = 0.01). (D) VtcaA showed no difference between heavy drinker and light drinker groups when VxA = VtcaA (P = 0.99). Values with error bars represent group mean ± SEM. Symbols represent individual concentrations; horizontal bars indicate the mean.