Northern Canadian populations (specifically the Inuit) display higher prevalence of diabetes and cardiovascular diseases. It is believed that diet and lifestyle contribute to the development of these disease; however, recent epidemiological studies suggest that persistent organic pollutants and heavy metals may also contribute to the development of these diseases. In this study, we outline the effects of these chemicals and the consumption of high fat/sugar food on glucose and cholesterol metabolism and lipoprotein signaling in JCR rat liver. Using gene profiler arrays, we have identified four genes that are affected mainly by these contaminants and/or diet. Our results indicate that these mixtures alter the expression of genes in gluconeogenesis pathway (fructose 1,6-bisphosphatase and pyruvate carboxylase), a protein involved in cholesterol transport (apolipoprotein A1), and a transcription factor that is responsible for the expression of proteins in lipogenesis pathway (sterol regulatory element binding transcription factor 1).