Longitudinal transcriptomic and metabolomic data demonstrate altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic rats

Fat metabolism is also peturbed after the diagnosis of type 1 diabetes. Patients have less fat in the liver (4) and increased fasting lipid oxidation (5) compared to controls. Similarly, in a BioBreeding rat model of type 1 diabetes, the diabetes-prone animals develop a reduced respiratory quotient compared to non-diabetic rats before the onset of hyperglycemia, consistent with an increased use of fatty acids relative to carbohydrates as an energy substrate (6). We hypothesized that a lack of insulin reaching the liver contributes to the metabolic shift towards lipid oxidation observed in humans with type 1 diabetes and rodent models of the disease. To test our hypothesis, we measured changes in the hepatic gene expression and serum metabolome of a BioBreeding rat model of type 1 diabetes before and after the onset of hyperglycemia. In this study, we investigate liver gene expression in BBDR.+/+, BBDR.lyp/lyp rat at day50 (+/-5 days) which are before hyperglycemic, and day55 (+/-5 days) which is short after hyperglycemic. Liver transcriptomes of 50 day old BBDR.lyp/lyp and 55 day old BBDR.+/+ rats were compared to 55 day old BBDR.lyp/lyp rats.