The type and quantity of dietary fat we ingest impacts the onset and progression of chronic diseases, e.g., atherosclerosis, diabetes and obesity. Our studies focus on the impact dietary fat has on hepatic gene expression, i.e., diet-gene interactions. Over the years we have defined mechanisms by which specific dietary fats regulate gene transcription by controlling the activity or abundance of key transcription factors. These transcription factors target genes involved in hepatic carbohydrate and lipid metabolism. Since the liver plays a central role in whole body carbohydrate and lipid metabolism, our studies reveal how diet can modify liver function, which in turn affects our health and the onset of metabolic diseases.