Brain Acetate and Ethanol Metabolism in Alcohol Dependence and Abuse
酒精依赖和滥用中的脑乙酸和乙醇代谢
基本信息
- 批准号:8701199
- 负责人:
- 金额:$ 53.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-07-15 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcetaldehydeAcetatesAcidsAcuteAlcohol abuseAlcohol consumptionAlcohol dependenceAlcoholic beverage heavy drinkerAlcoholsAstrocytesBase of the BrainBloodBlood - brain barrier anatomyBlood GlucoseBody WaterBrainBrain InjuriesCellsChemicalsComorbidityConsumptionDataDiabetes MellitusDropsDrug Metabolic DetoxicationEatingEnergy MetabolismEthanolEthanol MetabolismExposure toFailureGenerationsGlucoseGlutamatesGlutamineHeavy DrinkingHumanHypoglycemiaImpaired cognitionIndividualInfusion proceduresIngestionKetone BodiesLabelLifeLightLong-Term SurvivorsMeasuresMetabolismMonocarboxylic Acid TransportersNeurogliaNeuronsNutritionalPharmaceutical PreparationsPositioning AttributeRattusReactive Oxygen SpeciesRecording of previous eventsRecruitment ActivityRestRewardsRouteSourceStarvationSymptomsTestingTimeVascular blood supplyWithdrawalWorkaddictionalcohol effectbinge drinkingbrain pathwaydeprivationdrinkingfamily geneticsglobal healthinsulin secretionnovelnutritionoxidationpublic health relevancesobrietysugartrait
项目摘要
DESCRIPTION (provided by applicant): Alcohol abuse and dependence are global health concerns associated with numerous comorbidities. Hypoglycemia is a comorbidity particularly associated with binge-drinking. Under normal conditions glucose is the primary fuel for brain energy metabolism, so in hypoglycemia the brain relies increasingly on blood lactate, ketone bodies, and acetate, all of which cross the blood-brain barrier by the same monocarboxylic acid transporter. When drinking, the body converts alcohol to acetate, and the brain is able to utilize the acetate, partially replacing glucose consumption. Studies of hypoglycemia in diabetes and in starvation show that the transport and utilization of monocarboxylic acids are enhanced by hypoglycemia and by elevations in monocarboxlyic acids. Therefore, we hypothesize that through repeated exposure to elevated acetate and acute alcohol-induced hypoglycemia when not eating, heavy drinkers have a greater capacity to consume the acetate derived from ethanol than are light drinkers and non-drinkers. Our preliminary data support this hypothesis, and in this proposal we plan to test whether the condition is a state or a trait, by assessing if acetate consumption normalizes in alcohol-dependent people who have been sober for more than six months. We hypothesize that the heavy drinkers will consume more acetate than the light drinkers and long-term sober individuals. If the hypotheses of this project are supported, the fuel-generation aspect of alcohol may provide a novel reward mechanism that promotes the continuation of heavy drinking and helps to prolong episodes of binge-drinking. Another chemical derived from oxidation of alcohol is acetaldehyde, which is rewarding in the brain but aversive in the rest of the body. If the brain can derive energy not only from acetate, but also from the oxidation of ethanol within the brain, then the brain can generate acetaldehyde, creating another trigger to drink alcohol. We hypothesize that the brain does oxidize ethanol and that heavy drinkers oxidize more than light drinkers. If the human brain oxidizes ethanol, it provides a novel reward mechanism in humans, a mechanism that can be investigated with many approaches such as genetics and family history. These questions will be answered with 13C MRS during infusions of 13C-labeled acetate or ethanol.
描述(由申请人提供):酒精滥用和依赖是与多种合并症相关的全球健康问题。低血糖症是一种与暴饮暴食特别相关的合并症。在正常情况下,葡萄糖是大脑能量代谢的主要燃料,因此在低血糖症中,大脑越来越依赖于血乳酸、酮体和乙酸盐,所有这些都通过相同的单羧酸转运蛋白穿过血脑屏障。当饮酒时,身体将酒精转化为乙酸盐,大脑能够利用乙酸盐,部分取代葡萄糖消耗。对糖尿病和饥饿中低血糖的研究表明,低血糖和一元羧酸的升高可增强一元羧酸的转运和利用。因此,我们假设,通过反复暴露于升高的乙酸盐和急性酒精诱导的低血糖症时不吃,重度饮酒者有更大的能力消耗来自乙醇的乙酸盐比轻度饮酒者和非饮酒者。我们的初步数据支持这一假设,在这项提案中,我们计划通过评估戒酒超过六个月的酒精依赖者的醋酸盐消费是否正常化来测试这种情况是一种状态还是一种特征。我们假设重度饮酒者会比轻度饮酒者和长期清醒的人消耗更多的醋酸盐。如果该项目的假设得到支持,酒精的燃料生成方面可能提供一种新的奖励机制,促进酗酒的持续,并有助于延长暴饮暴食的发作。另一种来自酒精氧化的化学物质是乙醛,它在大脑中是有益的,但在身体的其他部分是令人厌恶的。如果大脑不仅可以从乙酸盐中获得能量,还可以从大脑内乙醇的氧化中获得能量,那么大脑就可以产生乙醛,从而产生另一种饮酒的触发因素。我们假设大脑确实会氧化乙醇,而且重度饮酒者比轻度饮酒者氧化得更多。如果人类大脑氧化乙醇,它为人类提供了一种新的奖励机制,这种机制可以通过遗传学和家族史等多种方法进行研究。在输注13C标记的醋酸盐或乙醇期间,将使用13C MRS回答这些问题。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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GRAEME F. MASON其他文献
GRAEME F. MASON的其他文献
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{{ truncateString('GRAEME F. MASON', 18)}}的其他基金
Relationship of Brain Ethanol Oxidation with Behavior
脑乙醇氧化与行为的关系
- 批准号:
10244983 - 财政年份:2020
- 资助金额:
$ 53.08万 - 项目类别:
Brain Acetate and Ethanol Metabolism in Alcohol Dependence and Abuse
酒精依赖和滥用中的脑乙酸和乙醇代谢
- 批准号:
9097473 - 财政年份:2013
- 资助金额:
$ 53.08万 - 项目类别:
Brain Acetate and Ethanol Metabolism in Alcohol Dependence and Abuse
酒精依赖和滥用中的脑乙酸和乙醇代谢
- 批准号:
8596244 - 财政年份:2013
- 资助金额:
$ 53.08万 - 项目类别:
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