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

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 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.