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: 8978008
• 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/8978008
• 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; Histones; 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; Translating; Translational Research; United States; United States National Institutes of Health; Universities; Unsaturated Fats; Work; alcohol abuse therapy; alcohol intervention; alcohol research; base; college; education research; high school; improved; inhibitor/antagonist; 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）的成立是为了作为一个区域/国家资源，以调查酒精引起的器官损伤的机制，并开发新的药物/干预措施，以预防/治疗这种器官损伤，这两个代表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：营养和酒精引起的器官损伤的作用。该方法是高度平移的。我们的调查人员包括来自13个部门和6所学院的教师。ULARC的具体目标是：1）促进跨学科的方法，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)提供一个强大的试点项目计划和全面的教育和研究培训，以培养下一代的酒精调查人员;和3）开发潜在的治疗目标/干预酒精诱导的器官损伤的基础上的机制研究的ULARC和翻译知识/干预社区。 我们将探讨营养和酒精滥用在酒精诱导的器官功能障碍发展中的相互作用，并评估各种潜在的营养治疗干预措施。项目（McClain/Kirpich）评估了饮食不饱和脂肪在酒精性肝病发展/进展中的作用。项目2（Barve/Feng）评价了酒精诱导的肠-肝轴改变。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，以及益生菌和饮食HDAC抑制剂在预防/治疗实验性ALD中的作用。项目3（Chen/Arteel）确定母亲饮酒导致后代智力迟钝的机制。他们评估了酒精诱导细胞凋亡和致畸作用的表观遗传机制，以及营养药萝卜硫素提供表观遗传保护的机制。项目4（Roman/沃森）评价酒精导致急性肺损伤易感性增加的机制。他们假设，慢性酒精摄入引发细胞外基质重塑，导致肺组织与促炎细胞外基质的“修复”，并且该过程可以通过饮食干预来调节。我们提出了3个试点，评估营养：酒精对A）肝脏，B）免疫系统和C）肠道：肝脏轴的相互作用，我们有一个新的“组学”核心（代谢组学/蛋白质组学），将被所有项目和试点利用，以及 酒精调查员/中心外。总之，这些项目形成了一个有凝聚力和互动的方法来调查营养和营养干预对酒精引起的器官损伤的影响。