Alcohol Consumption and Brown Adipose Tissue

酒精消耗和棕色脂肪组织

• 批准号: 8581336
• 负责人: WILLIAM S BLANER
• 金额: $ 18.43万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581336
• 关键词: Address; Adipocytes; Adjusted Life Years; Adolescent; Adult; Affect; Alcohol abuse; Alcohol consumption; Alcoholic Liver Diseases; Alcoholism; Alcohols; All-Trans-Retinol; American; Area; Biology; Body Temperature; Brown Fat; Cessation of life; Chronic; Coupled; Data; Diet; Disease; Disease Progression; Esters; Extrahepatic; Gene Expression; Genes; Heating; Hepatic; Homeostasis; Hospitalization; Hospitals; Human; Impairment; Individual; Injury; Laboratories; Liver; Maintenance; Mediating; Mediator of activation protein; Metabolic Diseases; Metabolism; Morbidity - disease rate; Morphology; Mus; Netherlands; Newborn Infant; Norepinephrine; Organ; Physical activity; Physiologic Thermoregulation; Physiological; Physiology; Process; Publishing; Reporting; Research; Research Proposals; Retinoids; Rodent; Series; Shivering; Stimulus; Techniques; Testing; Thermogenesis; Tissue Differentiation; Tissues; Vitamin A; Work; World Health Organization; adipocyte differentiation; alcohol effect; base; burden of illness; chronic alcohol ingestion; design; feeding; functional disability; global health; improved; innovation; insight; interest; natural hypothermia; novel; problem drinker; protein expression; public health relevance; research study; response; Address; Adipocytes; Adjusted Life Years; Adolescent; Adult; Affect; Alcohol abuse; Alcohol consumption; Alcoholic Liver Diseases; Alcoholism; Alcohols; All-Trans-Retinol; American; Area; Biology; Body Temperature; Brown Fat; Cessation of life; Chronic; Coupled; Data; Diet; Disease; Disease Progression; Esters; Extrahepatic; Gene Expression; Genes; Heating; Hepatic; Homeostasis; Hospitalization; Hospitals; Human; Impairment; Individual; Injury; Laboratories; Liver; Maintenance; Mediating; Mediator of activation protein; Metabolic Diseases; Metabolism; Morbidity - disease rate; Morphology; Mus; Netherlands; Newborn Infant; Norepinephrine; Organ; Physical activity; Physiologic Thermoregulation; Physiological; Physiology; Process; Publishing; Reporting; Research; Research Proposals; Retinoids; Rodent; Series; Shivering; Stimulus; Techniques; Testing; Thermogenesis; Tissue Differentiation; Tissues; Vitamin A; Work; World Health Organization; adipocyte differentiation; alcohol effect; base; burden of illness; chronic alcohol ingestion; design; feeding; functional disability; global health; improved; innovation; insight; interest; natural hypothermia; novel; problem drinker; protein expression; public health relevance; research study; response

DESCRIPTION (provided by applicant): This exploratory project will test the hypothesis that chronic alcohol consumption impairs the thermogenic capacity of brown adipose tissue (BAT), and that this impairment is associated with alcohol's effect on BAT retinoid metabolism. The project has two Specific Aims, the first is designed to assess the functional impairment associated with chronic alcohol consumption on BAT, and the second will provide mechanistic insight into the effects of alcohol in this tissue. The results of this project will be of broad significance to 3 research areas: research on alcoholism, BAT physiology, and retinoid homeostasis. The concept that BAT has physiological functions in adult humans represents a paradigm shift in the field of BAT research, and has led to an increased interest in this hitherto underappreciated tissue. Our preliminary data reveal that chronic alcohol consumption is associated with a dysregulation of body temperature maintenance, as well as a very marked decrease in BAT mass. In Specific Aim 1 the functional consequences of chronic alcohol consumption on BAT thermogenesis will be systematically investigated. Through a series of alcohol-feeding studies, we will assess the effects of alcohol-feeding on BAT morphology and function. The thermogenic capacity of alcohol-fed mice will be tested using 2 established techniques: responsiveness to cold exposure, and responsiveness to a norepinehprine challenge. We expect to establish that chronic alcohol consumption has a negative impact on the thermogenic capacity of BAT in adult mice. While Specific Aim 1 is designed to characterize the effect that alcohol feeding has on BAT function, Specific Aim 2 is designed to provide a mechanistic insight into this effect. Specifically, in Specific Aim 2 we will test the hypothesis tat alcohol-induced dysregulation of retinoid metabolism contributes to alcohol- induced alterations in BAT physiology. This hypothesis has its origins in the established effects that retinoids have on BAT differentiation and function, as well as our preliminary data which indicates that BAT of alcohol-fed mice has altered tissue retinoid levels, as well as changes in the gene expression levels of genes important in retinoid metabolism. We plan to undertake a comprehensive analysis of retinoid metabolism in BAT of alcohol-fed mice; we will also perform alcohol-feeding experiments in which the dietary retinoid content has been altered. We expect that the data obtained from these experiments will confirm our hypothesis that alcohol consumption disrupts BAT retinoid homeostasis, with a consequent effect on BAT function. In summary, the research proposed in this R21 application will explore the novel concept that chronic alcohol consumption affects the body's ability to produce heat through its effect on BAT. The data generated regarding these innovative hypotheses will impact general concepts regarding the effects of alcohol consumption on tissues other than the liver (specifically BAT), as well as provide mechanistic understanding of these changes.

描述（由申请人提供）：该探索性项目将检验以下假设：慢性酒精消耗会损害棕色脂肪组织（BAT）的热能能力，并且这种障碍与酒精对蝙蝠类维生素定型的影响有关。该项目具有两个特定的目标，第一个目的是评估与蝙蝠慢性酒精消耗相关的功能障碍，第二个将提供对酒精在该组织中的影响的机械洞察力。该项目的结果对3个研究领域具有广泛的意义：关于酒精中毒，BAT生理学和类维生素性稳态的研究。蝙蝠在成年人中具有生理功能的概念代表了蝙蝠研究领域的范式转变，并导致人们对迄今为止这种不足的组织的兴趣增加了。我们的初步数据表明，慢性酒精消耗与体温维持的失调以及蝙蝠质量的降低相关。在特定目标中，将系统地研究慢性酒精消耗对BAT热发生的功能后果。通过一系列饮酒研究，我们将评估饮酒对蝙蝠形态和功能的影响。酒精喂养小鼠的热能能力将使用2种既定的技术进行测试：对冷暴露的反应和对去甲型挑战的反应。我们希望确定慢性饮酒对成年小鼠蝙蝠的热能能力产生负面影响。虽然特定的目标1旨在表征酒精喂养对BAT功能的影响，但特定的AIM 2旨在提供对这种效果的机械洞察力。具体而言，在特定目标2中，我们将测试tat酒精诱导的类维生素性代谢失调的假设有助于酒精诱导的BAT生理学改变。该假设起源于视黄素对蝙蝠分化和功能的既定作用，以及我们的初步数据，表明酒精喂养的小鼠的蝙蝠改变了组织类维生素类动物的水平，以及在视黄素代谢中重要的基因表达水平的变化。我们计划对酒精喂养小鼠的蝙蝠进行类视感代谢进行全面分析；我们还将进行饮酒实验，其中饮食类维生素类似含量已改变。我们预计从这些实验获得的数据将证实我们的假设，即酒精消耗会破坏蝙蝠维生激素稳态，从而对BAT功能产生影响。总而言之，此R21应用程序中提出的研究将探讨一个新的概念，即长期饮酒会影响人体通过对蝙蝠的影响产生热量的能力。有关这些创新假设产生的数据将影响有关饮酒对肝脏以外的组织影响（特别是BAT）的影响的一般概念，并提供了对这些变化的机械理解。