Type 2 diabetes is a metabolic disorder which impacts hundreds of thousands of individuals. At a cellular level, the disease leads to altered insulin resistance, hyperglycemia, microvascular and macrovascular dysfunction, and increased fatty acids. These dysfunctions negatively impact tissue and organ function leading to an increase in morbidity and mortality in humans. We are interested in gaining a greater understanding of the impact hyperglycemia has on gene expression and cellular function. To study hyperglycemia we feed the genetic model system Caenorhabditis elegans a glucose-supplemented diet and examined the impact on gene expression and physiologic state. Previous studies show that C. elegans fed a glucose-supplemented diet had increased lipid accumulation and a significantly altered transcriptomic profile. One of the gene families that were impacted by a glucose diet include members of the nuclear hormone receptor (NHRs) family, which are involved in various molecular pathways including fatty acid metabolism. We conducted an RNA interference (RNAi) screen to examine if nuclear hormone receptor dysfunction impacted lipid content within the animal. In these experiments we assessed lipid levels using the oil red O technique. Our preliminary data suggests that dysfunctional nuclear hormone function is associated with an increase in lipid storage. Note that for these experiments the food availability was similar to that of control animals. This suggests that nuclear hormone receptor dysfunction impacts lipid storage levels. It remains to be determined if specific dysfunction of specific NHR associate with metabolic disorders including obesity and type 2 diabetes.