Location: Arkansas Children's Nutrition CenterTitle: Dietary fat source alters hepatic gene expression profile and determines the type of live pathology in rats overfed via total eteral nutrtion ) Author
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract only
Publication Acceptance Date: 2/13/2013
Publication Date: 4/15/2013
Citation: Ronis, M.J., Baumgardner, J., Marecki, J., Hennings, L., Wu, X., Shankar, K., Cleves, M., Gomez-Acevado, H., Badger, T.M. 2013. Dietary fat source alters hepatic gene expression profile and determines the type of live pathology in rats overfed via total eteral nutrtion [abstract]. FASEB Journal. 27(Meeting Abstracts):1072.2. Interpretive Summary:
Technical Abstract: Non-alcoholic fatty liver disease (NAFLD) is considered a part of the 'metabolic syndrome' associated with obesity and can progress in some patients to chirrosis, loss of liver function and liver cancer. NAFLD is now the most common form of liver injury, and rates are rising dramatically as a result of increasing obesity rates. However the biochemical and metabolic mechanisms underlying the development of fatty liver and progression of liver damage to inflammation and fibrosis and the nutritional factors affecting the severity of this disease remain unclear. Part of this is because there are few good animal models that replicate the clinical features of NAFLD and its progression. We have developed a new rat model of NAFLD in which we make the animals obese by overfeeding liquid diets via a stomach tube. This allows us to compare overfeeding diets of different types while keeping the total calories fed the same. In the current study, we used the TEN model to compare the effects of diets high in carbohydrate or high in three different types of unsaturated fats with different degrees of unsaturation (olive oil, corn oil, and echium oil). After 3 weeks of overfeeding high carbohydrate diets we observed fat accumulation in liver from rats fed high carbohydrate with olive oil and echium oil but not corn oil. This appeared due to differences in how fatty acids are stored and broken down in the liver of high carbohydrate/corn oil-fed animals. However, there was no evidence of progression of injury in any group fed high carbohydrates. In contrast, after feeding diets high in olive, corn, and echium oils, all livers were fatty, and liver injury was evident after overfeeding corn oil and echium oil both of which are polyunsaturated. In contrast, no evidence of cell death was evident after overfeeding olive oil (a monounsaturated fat) even though the livers were full of fat. Liver cell death after corn oil or echium oil was accompanied by an increase in fatty acid breakdown products previously associated with development of liver injury in NAFLD patients clinically. These data suggest that although diets such as the Mediterranean Diet high in monounsaturated fats like olive oil may produce fatty liver, these livers appear to be protected against further injury as a result of the inability of monounsaturated fats compared to polyunsaturated fats to be attacked and broken down by oxygen radicals.