P0129DIET INDUCED ACCELERATION OF RENAL INJURY IN THE BTBROB/OB MOUSE MODEL OF DIABETIC KIDNEY DISEASE

Abstract Background and Aims There is a need of disease relevant models for efficient evaluation of new drug targets in the renal field. The obese diabetic BTBRob/ob mouse model have features resembling important aspects of human diabetic kidney disease and is extensively used in pharmacological studies. Since diet composition plays a role in diabetic- and renal disease it is important to have detailed control of nutritional intake in our pre-clinical models, especially since many studies use in-diet drug administration. In this study we compared disease progression in obese diabetic mice on non-defined chow diet (R3) with the defined control diet D12450B (Research Diets). Method BTBRob/ob mice were fed either regular laboratory rodent chow (R3) or the defined control diet D12450B containing 35% sucrose from 6 weeks of age. The animals were studied for 14 to 20 weeks of age and both physical parameters, urine and blood parameters, histology and gene expression was examined. (R3 group n=14, D12450B group n=8). Results Mice on the defined D12450B diet displayed increased calorie- and water intake, but gained less weight compared to R3 group. Blood glucose and HbA1c was higher at all timepoints, and urinary albumin-to-creatinine ratio was highly elevated compared to mice on R3 diet. Mice fed D12450B also displayed lower levels of plasma insulin and increased plasma b-hydroxybutyrate levels. Histopathological evaluation revealed that the defined D12450B diet increased induction both of mesangial injury score and gene expression of tubular injury markers NGAL and Kim-1. Conclusion : In summary, the choice of diet composition will have a huge impact on the disease progression in diabetic leptin-deficient overeating mouse models. These finding underline the importance of describing the diet composition in detail and take precaution on diet selection for preclinical studies.