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Obesity and type 2 diabetes mellitus (T2DM) are occurring at epidemic-like rates, and these epidemics appear to have emerged largely from changes in daily diet. In the present study, we compared effects of high-fat diet (HFD) and fructose-rich diet (FRD) in WBN/Kob-Lepr fa (WBKDF) rats that spontaneously develop obesity, dyslipidemia and T2DM. After a 4-week feeding of each diet, WBKDF-HFD and WBKDF-FRD rats exhibited aggravated obesity and dyslipidemia compared with WBKDF rats fed standard diet (STD). In contrast, hyperglycemia developed in WBKDF-STD rats was significantly inhibited in WBKDF-FRD rats, but not in WBKDF-HFD rats. The present study demonstrated that the 4-week feeding of HFD and FRD caused diet-induced obesity with a distinct phenotype in the glucose metabolism in WBKDF rats.

WBN/Kob-Lepr(fa) (fa/fa) rats have been identified as a new animal model of type 2 diabetes (T2DM), as they are characterized by impaired pancreatic insulin secretion and severe insulin resistance. Our previous study demonstrated impaired insulin secretion and its involvement in hyperglycemia in fa/fa rats. The present study was aimed at elucidating the role of insulin resistance in the development and progression of diabetes in these animals. Troglitazone (TGZ) was used as an insulin sensitizer. Insulin resistance and insulin secretory capacity were measured by a homeostasis model assessment of insulin resistance and the area under the blood concentration-time curve for plasma insulin levels after intravenous glucose tolerance testing, respectively. The fa/fa rats exhibited marked insulin resistance between 5 and 11 weeks of age, compared with age-matched Wistar rats. The insulin secretory capacity of fa/fa rats was higher than that of Wistar rats at 5 weeks of age, but decreased by 50% between 9 and 11 weeks of age. The fa/fa rats were fed a standard diet, with or without 0.2% w/w TGZ, for 4 weeks. Treatment with TGZ significantly improved insulin resistance, hyperglycemia and hypertriglyceridemia in both prophylactic and therapeutic study groups. These results suggest that insulin resistance is markedly involved in the development and progression of T2DM in fa/fa rats.

The aim of this study was to investigate blood coagulation times in genetically obese rats and diet-induced obese (DIO) mice in order to clarify the relationship between visceral obesity and blood coagulation. WBN/Kob-Lepr(fa) (fa/fa) rats, a genetically obese model, exhibited a significantly shorter activated partial thromboplastin time (aPTT) and prothrombin time (PT) than age-matched Wistar rats. C57BL/6J mice fed a high-fat diet (60%), a DIO model, exhibited significantly shorter aPTT, PT and thrombin time than lean mice fed a standard diet. Higher body weight, visceral fat weight and insulin resistance were also shared by fa/fa rats and DIO mice. These results suggest that visceral obesity is related to accelerated blood coagulation in addition to disrupted metabolism of glucose and lipids.