Acute alcohol intoxication decreases glucose metabolism but increases acetate uptake in the human brain

Volkow, Nora D.; Kim, Sung Won; Wang, Gene‐Jack; Alexoff, David; Logan, Jean; Muench, Lisa; Shea, Colleen; Telang, Frank; Fowler, Joanna S.; Wong, Christopher; Benveniste, Helene; Tomasi, Dardo

doi:10.1016/j.neuroimage.2012.08.057

Cited by 94 publications

(104 citation statements)

References 48 publications

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“…Such impact of transport, facilitating some conversion from glucose to acetate consumption, would be consistent with recent data that show that the rat brain decreases uptake and phosphorylation of glucose when the acetate levels are higher in the blood (31). Human results also show decreased glucose uptake and higher acetate consumption in the presence of alcohol (30). An important but challenging measurement to make in these populations would be blood-brain transport of acetate.…”

Section: Figuresupporting

confidence: 84%

“…Although acetate metabolism has been characterized in situations other than drinking, links between acetate metabolism and alcohol consumption are not clear. Recent data show that alcohol decreases brain glucose utilization (29)(30)(31) and increases acetate uptake (30). These findings lead to our hypothesis: upon chronic heavy alcohol intake, brain can use more acetate as a source of energy.…”

Section: Introductionmentioning

confidence: 67%

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Increased brain uptake and oxidation of acetate in heavy drinkers

Jiang

Gulanski²,

Feyter³

et al. 2013

J. Clin. Invest.

119

114

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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 13 C 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 [2-13 C]acetate for 2 hours and scanned throughout that time with magnetic resonance spectroscopy of the brain to observe natural 13 C abundance of N-acetylaspartate (NAA) and the appearance of 13 C-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.

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Section: Figuresupporting

confidence: 84%

Section: Introductionmentioning

confidence: 67%

Increased brain uptake and oxidation of acetate in heavy drinkers

Jiang

Gulanski²,

Feyter³

et al. 2013

J. Clin. Invest.

119

114

View full text Add to dashboard Cite

show abstract

“…Acetate (Ac) generated from Etoh by the liver is consumed by the brain (3,4), where it replaces a significant portion of cerebral glucose metabolism in humans and animals (5)(6)(7)(8), either decreasing glucose consumption directly or compensating for glucose consumption decreased by some other effect. However, the brain may also oxidize Etoh (9)(10)(11)(12)(13)(14), and that capacity is important with respect to several perspectives.…”

mentioning

confidence: 99%

Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure

Wang

Jiang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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It has been reported that chronic and acute alcohol exposure decreases cerebral glucose metabolism and increases acetate oxidation. However, it remains unknown how much ethanol the living brain can oxidize directly and whether such a process would be affected by alcohol exposure. The questions have implications for reward, oxidative damage, and long-term adaptation to drinking. One group of adult male Sprague-Dawley rats was treated with ethanol vapor and the other given room air. After 3 wk the rats received i.v. [2-13 C]ethanol and [1, 2-13 C 2 ]acetate for 2 h, and then the brain was fixed, removed, and divided into neocortex and subcortical tissues for measurement of 13 C isotopic labeling of glutamate and glutamine by magnetic resonance spectroscopy. Ethanol oxidation was seen to occur both in the cortex and the subcortex. In ethanol-naïve rats, cortical oxidation of ethanol occurred at rates of 0.017 ± 0.002 μmol/min/g in astroglia and 0.014 ± 0.003 μmol/min/g in neurons, and chronic alcohol exposure increased the astroglial ethanol oxidation to 0.028 ± 0.002 μmol/min/g (P = 0.001) with an insignificant effect on neuronal ethanol oxidation. Compared with published rates of overall oxidative metabolism in astroglia and neurons, ethanol provided 12.3 ± 1.4% of cortical astroglial oxidation in ethanol-naïve rats and 20.2 ± 1.5% in ethanol-treated rats. For cortical astroglia and neurons combined, the ethanol oxidation for naïve and treated rats was 3.2 ± 0.3% and 3.8 ± 0.2% of total oxidation, respectively. 13C labeling from subcortical oxidation of ethanol was similar to that seen in cortex but was not affected by chronic ethanol exposure.T he liver is the major organ for the oxidation of ethanol (Etoh) (1, 2), followed by the stomach and other organs. Acetate (Ac) generated from Etoh by the liver is consumed by the brain (3, 4), where it replaces a significant portion of cerebral glucose metabolism in humans and animals (5-8), either decreasing glucose consumption directly or compensating for glucose consumption decreased by some other effect. However, the brain may also oxidize Etoh (9-14), and that capacity is important with respect to several perspectives. The first step of Etoh oxidation generates acetaldehyde (AA), which is toxic, reactive, and potentially carcinogenic. AA is aversive systemically, as has been observed from the unpleasant effects of disulfuram, an inhibitor of AA dehydrogenase, but it has been shown to be rewarding in parts of the brain (12,15,16) especially in the posterior ventral tegmental area (17-19) by activating dopamine neurons (20)(21)(22). The liver maintains circulating levels of AA at levels of 20-155 μM (23, 24), and AA has been reported not to penetrate the blood-brain barrier or to penetrate very slowly (23,25). Thus, if the brain can oxidize Etoh, then intracerebral AA may mediate behavioral, neurochemical, and toxic effects of Etoh in the brain, possibly playing a role in the development of alcohol dependence (6,16,26).AA is difficult to measure in living systems. The ...

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“…These methods use spectroscopic techniques, such as magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) 13,14 or positron emission tomography (PET), which are principally used to monitor ethanol metabolites 15 . The aim of this review is to show and critically discuss all the techniques used to monitor brain ethanol and highlight their strengths and weaknesses.…”

Section: Biosensingmentioning

confidence: 99%