Pathophysiological Changes With Aging in a Novel Obese Diabetic Rat

The Spontaneously Diabetic Torii (SDT) fatty rat develops hyperglycemia and dyslipidemia from a young age, leading to diabetic complications, such as nephropathy, retinopathy, neuropathy, and non-alcoholic steatohepatitis (NASH). In this study, we investigated pathophysiological changes in female SDT fatty rats at 65 weeks. Hyperglycemia and hyperlipidemia were sequentially observed in the rats, and blood insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also increased. Histopathological analyses were performed in the liver, kidney, heart and eye. Pathological findings, such as focal and/or diffuse hypertrophied hepatocytes with fatty changes, and very slight inflammation and fibrosis in the liver, were observed in the rats. Glomerular and tubular lesions in the kidney and corneal lesions were also observed; however, the NASH-like lesions tended to diminish compared with those at 40 weeks. As new findings associated with age, corneal lesions such as inflammation, vascularization and fibrosis, and increased cardiac fibrosis were observed in the aging rats. The aging female SDT fatty rat may be useful in better understanding the pathophysiology and development of new therapies in chronic kidney disease (CKD), diabetic ocular lesions and diabetic cardiomyopathy. Diet manipulation is also necessary for the acceleration of characteristic diseases.

                               

Diabetes mellitus and obesity are common metabolic disorders, and this population of patients is rapidly increasing worldwide. Among the factors related to the increasing prevalence of this disease are consumption of high calorie diets and sedentary lifestyles. Furthermore, the growing population of patients with diabetes and obesity has resulted in a rapid increase in the number of patients who have diabetic complications, such as nephropathy, retinopathy, and neuropathy. Despite efforts to develop means to suppress or treat the incidence and progression of these diseases, the effects and results remain poor. Various animal models for diabetes and obesity have been established to help better understanding the pathophysiology in metabolic diseases and to develop new therapies. 

The Spontaneously Diabetic Torii (SDT) fatty rat was established by

introducing the fa allele of the Zucker fatty rat into the nonobese SDT rat genome. The SDT fatty rat develops obesity, hyperglycemia, and dyslipidemia at a young age. Furthermore, with the early incidence of diabetes, diabetes-related complications in the SDT fatty rat are seen at a younger age compared with other obese diabetic models. However, we have not examined the long-term changes of diabetic complications, keep, deterioration, or remission. In this study, we investigated the pathophysiological changes in the aging female SDT fatty rat.