Diet is a central environmental factor that contributes to the phenotype and physiology of individuals. At the root of many human health issues is the excess of calorie intake relative to calorie expenditure. For example, the increasing amount of dietary sugars in the human diet is contributing to the rise of obesity and type 2 diabetes. Individuals with obesity and type 2 diabetes have compromised oxygen delivery, and thus it is of interest to investigate the impact a high-sugar diet has on oxygen deprivation responses. By utilizing the Caenorhabditis elegans genetic model system, which is anoxia tolerant, we determined that a glucose-supplemented diet negatively impacts responses to anoxia and that the insulin-like signaling pathway, through fatty acid and ceramide synthesis, modulates anoxia survival. Additionally, a glucose-supplemented diet alters lipid localization and initiates a positive chemotaxis response. Use of RNA-sequencing analysis to compare gene expression responses in animals fed either a standard or glucose-supplemented diet revealed that glucose impacts the expression of genes involved with multiple cellular processes including lipid and carbohydrate metabolism, stress responses, cell division, and extracellular functions. Several of the genes we identified show homology to human genes that are differentially regulated in response to obesity or type 2 diabetes, suggesting that there may be conserved gene expression responses between C. elegans fed a glucose-supplemented diet and a diabetic and/or obesity state observed in humans. These findings support the utility of the C. elegans model for understanding the molecular mechanisms regulating dietary-induced metabolic diseases.KEYWORDS sugar diet; oxygen deprivation; insulin signaling; gene expression; C. elegans T HE chronic and excessive intake of calories relative to daily energy expenditure often results in major heath issues such as obesity, metabolic syndrome, and type 2 diabetes (Ogden et al. 2012;Sonestedt et al. 2012). A recent change in the Western human diet, in comparison to traditional diets of the past, has been an increase in dietary saturated fats and sugars (e.g., sugar-sweetened beverage intake rose 135% between 1977 and 2001) (de Koning et al. 2011). Glucose, which is an essential component of metabolism and energy production, induces pancreatic b-cells to secrete insulin, which in turn facilitates the import of glucose into tissues such as muscle and adipose. However, a chronic overabundance of glucose and/or fructose will have deleterious effects on cellular and tissue functions. For example, an excess of dietary sugar leads to the inability of cells to respond correctly to insulin (insulin resistance), resulting in a decrease in glucose uptake by cells and an increase in glucose remaining within the circulatory system (hyperglycemia) (Brownlee 2001;Szablewski 2011). An excess of dietary sugars increases adipose tissue, triglycerides, and low-density lipoproteins (Szablewski 2011). An additional consequence of hype...

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