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Diet-Disease Interactions at the Molecular Level: An Experimental Paradigm1,2,

Jim Kaput, Deborah Swartz, Elizabeth Paisley, Heather Mangian, William L. Daniel and Willard J. Visek

Department of Internal Medicine, University of Illinois College of Medicine, Urbana, Illinois 61801

High levels of dietary fat enhance the severity of certain cancers, obesity, and cardiovascular diseases in susceptible individuals usually after prolonged exposure. We have been developing methods for identifying and characterizing genes regulated by the level of dietary fat for the purpose of determining their role in diseases promoted by high levels of dietary fat, particularly cancer and atherosclerosis. Our protocol employs semi-purified diets of reproducible composition fed to normal inbred mice to obtain reagents for studying of molecular events that lead to pathology. Our early studies demonstrated that different levels of dietary fat cause the accumulation or change in expression of two genes, designated Lfm-1 and Lfm-2 (low fat mammary) in mouse mammary glands and selected other tissues. The Lfm-2 gene is stearoyl CoA desaturase, a gene known to be regulated by dietary fat and insulin levels. The Lfm-1 gene is highly similar to the e subunits of bovine and rat F1F0-ATPases. A Lfm-1 restriction fragment length polymorphism located on chromosome 8 is associated with atherosclerosis in certain inbred strains of mice warranting additional tests to determine whether it is involved in initiation or promotion of heart disease. The experimental approach has the potential for analyzing genes regulated by approximately 50 essential nutrients or other dietary constituents. A potential outcome of this research is the development of reagents which can be used to predict the risk of diet-related diseases in individuals.


KEY WORDS: • gene expression • atherosclerosis • cancer • genetics

1 This research was supported by funds from a USDA Grant (91-01631), the Department of Food Sciences, and the Colleges of Agriculture and Medicine at the University of Illinois. D.S. was supported by NIH Training Grant (PHS 5T32-AM07497) and an American Institute of Nutrition Predoctoral Fellowship. E.P. is an American Institute of Nutrition Predoctoral Fellow.

2 Presented as part of the symposium "Dietary Fat and Gene Expression," given at the Experimental Biology '93 meeting, New Orleans, LA March 28–April 1, 1993. The symposium was sponsored by the American Institute of Nutrition and the American Society for Clinical Nutrition. The guest editor for this symposium was Willard J. Visek, Department of Internal Medicine, University of Illinois College of Medicine, Urbana, IL.




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