Histopathological analyses of diabetic nephropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats

Background: Otsuka Long-Evans Tokushima fatty (OLETF) rats are an established model of diabetic nephropathy. However, diabetes and diabetic nephropathy (DN) in OLETF rats develop later than in other animal type 2 diabetes models. Objectives: This study was conducted to investigate the serial changes in the histopathological characteristics of DN in sucrose-fed OLETF rats by biochemical and morphometric analyses. Methods: We conducted sucrose feeding to examine the progression of DN. One group of OLETF rats was given water containing 30% sucrose ad libitum (SO) and the other group was given water without 30% sucrose (TO). Consecutive observations were made at 4-week intervals from 16 to 50 weeks of age in TO rats, and from 16 to 42 weeks of age in SO rats. Examination parameters included body weight, serum glucose level, urine albumin-to-creatinine ratio (UACR), light microscopy (LM) and electron microscopy (EM). Results: The UACR was over 300 mg/g in 32-week-old SO rats (after 16 weeks of sucrose feeding) and in 38-week-old TO rats. LM indicated that glomerular hypertrophy and mesangial matrix expansion in SO rats increased compared to that of age-matched TO rats especially at 42 weeks of age (p<0.05). EM also showed that glomerular basement membrane thickness and podocyte foot process width of SO rats were significantly greater than those of age-matched TO rats (p<0.05). Conclusion: Our results suggested that dietary manipulation by sucrose feeding may cause deterioration of DN and could hasten the onset of diabetes and DN in OLETF rats.