DIET-DISEASE INTERACTIONS AT THE MOLECULAR-LEVEL - AN EXPERIMENTAL PARADIGM

High levels of dietary fat enhance the severity of certain cancers, ob esity, and cardiovascular diseases in susceptible individuals usually after prolonged exposure. We have been developing methods for identify ing and characterizing genes regulated by the level of dietary fat for the purpose of determining their role in diseases promoted by high le vels of dietary fat, particularly cancer and atherosclerosis. Our prot ocol employs semi-purified diets of reproducible composition fed to no rmal inbred mice to obtain reagents for studying of molecular events t hat lead to pathology. Our early studies demonstrated that different l evels of dietary fat cause the accumulation or change in expression of two genes, designated Lfm-1 and Lfm-2 (low fat mammary) in mouse mamm ary glands and selected other tissues. The Lfm-2 gene is stearoyl CoA desaturase, a gene known to be regulated by dietary fat and insulin le vels. The Lfm-1 gene is highly similar to the e subunits of bovine and rat F1F0-ATPases. A Lfm-1 restriction fragment length polymorphism lo cated on chromosome 8 is associated with atherosclerosis in certain in bred strains of mice warranting additional tests to determine whether it is involved in initiation or promotion of heart disease. The experi mental approach has the potential for analyzing genes regulated by app roximately 50 essential nutrients or other dietary constituents. A pot ential outcome of this research is the development of reagents which c an be used to predict the risk of diet-related diseases in individuals .