Molecular analyses of differences in gene expression due to changes in the level of dietary fat

Dietary fat has been shown to exacerbate important chronic diseases including, heart disease, obesity, hyperlipidemia, diabetes and cancer. This thesis described studies carried out to further our understanding of genes whose expression is altered by the level of dietary fat. The experimental approach was designed to obtain basic information in virgin female mice whose responses to dietary fat were not confounded by the production of a mammary tumor virus, hormonal events of pregnancy or the use of a chemical carcinogen. I have used molecular biology techniques to identify genes regulated by different levels of dietary fat. cDNA libraries were constructed from mammary tissue of virgin female Balb/c mice (7wks) fed a fat free diet for one week and then switched to either a 3 or 20% corn oil (co) diet for 2 wks. Subtractive hybridization of the lowfat cDNA library revealed genes expressed preferentially by mice fed the 3% co diet. These clones are designated lowfat mammary 1 and 2 (LFM-1, LFM-2). The diet regulated LFM-1 is a homolog to an UV-inducible gene. Since DNA repair enzymes are also induced by UV-irradiation, the identification of this single gene suggests that genes involved in DNA repair also may be regulated by dietary fat. Regulation of DNA repair genes by different levels of dietary fat may provide the first experimental link between the high fat diet and promotion of specific diseases.The second diet-specific cDNA, LFM-2, had homology to stearoyl-CoA-desaturase (SCD) which is the rate-limiting step in the de novo synthesis of unsaturated fatty acids from acetyl-CoA in animal tissues. The regulation of SCD by dietary fat is not well understood at this time. The physiological importance of SCD is probably related to the production of oleic acid which is the major fatty acid constituent in mouse depot fat. In conclusion, the data presented in this thesis showed that different levels of dietary fat as 3 and 20% corn oil, can modulate the expression of specific genes. The identification of diet regulated genes will be useful in gaining understanding of the influence of macronutrients on tissue physiology and development.U of I OnlyETDs are only available to UIUC Users without author permissio