The Role of Nutrition in the Development/Progression of Alcohol-Induced Organ Injury

营养在酒精引起的器官损伤的发生/进展中的作用

• 批准号: 9273306
• 负责人: CRAIG J. MCCLAIN
• 金额: $ 153.25万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9273306
• 关键词: Acute Lung Injury; Alcohol Nutrition; Alcohol abuse; Alcohol consumption; Alcoholic Liver Diseases; Alcohols; Apoptosis; Area; Award; Biomedical Engineering; Carnosine; Cause of Death; Chronic; Clinical Research; Collaborations; Communities; Development; Diet; Dietary Intervention; Education; Epigenetic Process; Extracellular Matrix; FDA approved; Faculty; Functional disorder; Funding; Goals; Health; Health Care Costs; Histone Deacetylase; Histone Deacetylase Inhibitor; Immune system; Industry; Injury; Institution; Intervention; Intestines; Knowledge; Laboratories; Lead; Lipids; Liver; Mental Retardation; Morbidity - disease rate; National Institute on Alcohol Abuse and Alcoholism; New Agents; Nutraceutical; Nutritional; Organ; Pilot Projects; Predisposition; Prevention; Probiotics; Process; Proteomics; Research; Research Personnel; Research Training; Resources; Rewards; Role; S-Adenosylmethionine; Steatohepatitis; Structure of parenchyma of lung; Sulforaphane; Therapeutic Intervention; Training and Education; Translating; Translational Research; United States; United States National Institutes of Health; Universities; Unsaturated Fats; alcohol abuse therapy; alcohol intervention; alcohol research; base; cohesion; college; high school; improved; interdisciplinary approach; interest; metabolomics; mortality; multidisciplinary; new therapeutic target; next generation; novel; nutrition; offspring; prevent; programs; public health relevance; success; therapeutic target

 DESCRIPTION (provided by applicant): The University of Louisville Alcohol Research Center (ULARC) was created to serve as a regional/national resource to investigate mechanisms of alcohol induced organ injury and to develop new agents/interventions to prevent/treat this organ injury, both of which represent important unmet research needs. The theme of the center is unique among alcohol centers: the role of nutrition and alcohol-induced organ injury. The approach is highly translational. Our investigators include faculty from 13 departments and 6 colleges. The Specific Aims of the ULARC are to: 1) facilitate interdisciplinary approaches and serve as a regional/national resource for the study of nutrition and alcohol-induced organ injury; 2) provide a robust pilot project program and comprehensive education and research training in order to develop the next generation of alcohol investigators; and 3) develop potential therapeutic targets/interventions for alcohol induced organ injury based on the mechanistic research of the ULARC and translate knowledge/interventions to the community. We will explore interactions of nutrition and alcohol abuse in the development of alcohol-induced organ dysfunction, and we will evaluate diverse potential nutritional therapeutic interventions. Project (McClain/Kirpich) evaluates the role of dietary unsaturated fat in the development/progression of alcoholic liver disease. Project 2 (Barve/Feng) evaluates alcohol-induced alterations in the gut-liver axis. They study the role of histone deacetylases (HDACs) in both the intestine and liver in gut-barrier dysfunction and steatohepatitis and the role of probiotics and dietary HDAC inhibitor in preventing/treating experimental ALD. Project 3 (Chen/Arteel) determines mechanisms by which maternal alcohol consumption causes mental retardation in the offspring. They evaluate epigenetic mechanisms by which alcohol induces apoptosis and teratogenesis, and by which the nutraceutical, sulforaphane, provides epigenetic protection. Project 4 (Roman/Watson) evaluates mechanisms by which alcohol causes increased susceptibility to acute lung injury. They postulate that chronic alcohol intake triggers extracellular matrix remodeling resulting in "repavement" of lung tissue with a proinflammatory extracelluar matrix and that this process can be modulated by dietary intervention. We propose 3 pilots that evaluate nutrition:alcohol interactions on the A) liver, B) immune system, and C) the gut:liver axis, and we have a novel "omics" core (metabolomics/proteomics) that will be utilized by all projects and pilots, as well as outside alcohol investigators/centers. Together, these projects form a cohesive and interactive approach to investigate the effects of nutrition and nutritional interventions on alcohol-induced organ injury.

 描述（由申请人提供）：路易斯维尔大学酒精研究中心 (ULARC) 的成立是为了作为地区/国家资源来研究酒精引起的器官损伤的机制，并开发新的药物/干预措施来预防/治疗这种器官损伤，这两者都代表了重要的未满足的研究需求。该中心的主题在酒精中心中是独一无二的：营养的作用和酒精引起的器官损伤。该方法具有高度转化性。我们的调查人员包括来自 13 个系和 6 个学院的教师。 ULARC 的具体目标是： 1) 促进跨学科方法并作为营养和酒精引起的器官损伤研究的区域/国家资源； 2) 提供强有力的试点项目计划和全面的教育和研究培训，以培养下一代酒精调查员； 3) 基于 ULARC 的机制研究，开发酒精引起的器官损伤的潜在治疗靶点/干预措施，并将知识/干预措施转化为社区。 我们将探讨营养和酒精滥用在酒精引起的器官功能障碍发展中的相互作用，并将评估各种潜在的营养治疗干预措施。项目（McClain/Kirpich）评估膳食不饱和脂肪在酒精性肝病发生/进展中的作用。项目 2（Barve/Feng）评估酒精引起的肠-肝轴变化。他们研究了肠道和肝脏中组蛋白脱乙酰酶 (HDAC) 在肠道屏障功能障碍和脂肪性肝炎中的作用，以及益生菌和膳食 HDAC 抑制剂在预防/治疗实验性 ALD 中的作用。项目 3（Chen/Arteel）确定了母亲饮酒导致后代智力低下的机制。他们评估了酒精诱导细胞凋亡和畸形发生的表观遗传机制，以及营养保健品萝卜硫素提供表观遗传保护的机制。项目 4（Roman/Watson）评估酒精导致急性肺损伤易感性增加的机制。他们假设，长期饮酒会触发细胞外基质重塑，导致肺组织被促炎细胞外基质“修复”，并且这一过程可以通过饮食干预来调节。我们提出了 3 个试点项目来评估营养：酒精对 A) 肝脏、B) 免疫系统和 C) 肠道：肝轴的相互作用，并且我们有一个新颖的“组学”核心（代谢组学/蛋白质组学），将被所有项目和试点项目以及 外部酒精调查员/中心。这些项目共同形成了一种有凝聚力和互动的方法，以研究营养和营养干预对酒精引起的器官损伤的影响。