Alcohol Consumption and Brown Adipose Tissue

酒精消耗和棕色脂肪组织

• 批准号: 8459054
• 负责人: WILLIAM S BLANER
• 金额: $ 23万
• 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/8459054
• 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

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）：该探索性项目将测试以下假设：长期饮酒会损害棕色脂肪组织 (BAT) 的产热能力，并且这种损害与酒精对 BAT 类视黄醇代谢的影响有关。该项目有两个具体目标，第一个目标是评估与慢性饮酒相关的 BAT 功能损伤，第二个目标是深入了解酒精对该组织的影响。该项目的成果将对酗酒、BAT 生理学和类视黄醇稳态研究 3 个研究领域具有广泛意义。 BAT 在成年人中具有生理功能的概念代表了 BAT 研究领域的范式转变，并导致人们对这种迄今为止未被充分认识的组织越来越感兴趣。我们的初步数据显示，长期饮酒与体温维持失调以及 BAT 质量显着下降有关。在具体目标 1 中，将系统地研究长期饮酒对 BAT 生热作用的功能影响。通过一系列的酒精喂养研究，我们将评估酒精喂养对BAT形态和功能的影响。将使用两种已建立的技术来测试酒精喂养小鼠的生热能力：对寒冷暴露的反应性和对去甲肾上腺素挑战的反应性。我们期望确定长期饮酒对成年小鼠 BAT 的产热能力有负面影响。具体目标 1 旨在描述饮酒对 BAT 功能的影响，而具体目标 2 旨在提供对这种影响的机制洞察。具体来说，在具体目标 2 中，我们将检验以下假设：酒精引起的类视黄醇代谢失调会导致酒精引起的 BAT 生理学改变。这一假设源于类视黄醇对 BAT 分化和功能的既定影响，以及我们的初步数据表明，酒精喂养的小鼠的 BAT 改变了组织类视黄醇水平，以及基因的基因表达水平的变化在类维生素A代谢中很重要。我们计划对酒精喂养小鼠的 BAT 中的类视黄醇代谢进行全面分析；我们还将进行酒精喂养实验，其中饮食中的类视黄醇含量已被改变。我们期望从这些实验中获得的数据将证实我们的假设，即饮酒会破坏 BAT 类视黄醇稳态，从而对 BAT 功能产生影响。总之，R21 申请中提出的研究将探索一个新概念，即长期饮酒通过影响 BAT 来影响身体产生热量的能力。关于这些创新假设生成的数据将影响关于饮酒对肝脏以外的组织（特别是 BAT）影响的一般概念，并提供对这些变化的机制理解。