ABSTRACT
Aim: Sex hormones, including testosterone and estrogen, result in various pathophysiological changes in the body. To evaluate the pathophysiological changes following gonadectomy in male and female rats, we performed gonadectomy at the same age in male and female Sprague-Dawley (SD) rats. Methods: Male and female Sprague-Dawley rats castrated by bilaternal orchidectomy and ovariectomy at 6 weeks of age (six animals of each sex per group). Food intake, body weight, and clinical chemical parameters such as glucose, insulin, triglyceride and total cholesterol levels, were examined every 4 weeks from 8 to 40 weeks of age. Statistical analysis of differences between control and gonadectomized rats was performed using the F-test, followed by the Student’s t-test or Aspin-Welch’s t-test. Results: In orchidectomized (ORX) rats, food intakes and body weights were decreased, whereas in ovariectomized (OVX) rats, the body weights were significantly elevated without an obvious change in food intake. In clinical chemical analysis, hypercholesterolemia was observed in both ORX and OVX rats, but the triglyceride level was obviously decreased only in ORX rats during the observational period. In OVX rats, decrease of insulin sensitivity and significant increase of adipose tissue weights were observed. In bone metabolic analysis, bone mineral content in ORX rats and bone mineral density in OVX rats were decreased, respectively. Conclusion: Both orchidectomy and ovariectomy in rats affect glucose/lipid and bone metabolism, and especially, the glucose metabolism was deteriorated in OVX rats. Both male and female sex hormones play a key role in metabolic disease, such as diabetes, hyperlipidemia and osteoporosis.
ABSTRACT
Aim: Reduced calorie intake by food restriction leads to extension of life span by exerting beneficial effects on metabolism. Zucker diabetic fatty (ZDF) rat is a type 2 diabetic model with obesity, showing the incidence of diabetes after 7 weeks of age. The present study investigated effects of 2-week food restriction on the pancreas in ZDF rats. Methods: ZDF rats were pair-fed with Zucker lean (ZL) rats from 7 to 9 weeks of age (The amount of food in ZDF rats was calculated based on the daily food consumption in ZL rats). Body weight and biochemical parameters such as serum glucose, triglyceride, total cholesterol, non-esterified fatty acid and insulin levels, were evaluated. After necropsy, islet size and insulin content in pancreas were measured. Results: The ZDF rats showed increased blood glucose, insulin and lipid levels at 7 weeks as compared with those in ZL rats. After food restriction for 2 weeks, the blood glucose, insulin, and triglyceride levels in pair-fed ZDF rats were decreased. The islet size in pair-fed ZDF rats decreased as compared with that in ad lib-fed ZDF rats, but the insulin content in pancreas of pair-fed ZDF rats increased remarkably. Conclusion: ZDF rats showed improvement of pancreatic disorders by food restriction. Caloric restriction applied at an insulin resistant pre-diabetic stage is an effective means for preventing the pancreatic disorder in diabetes with obesity.
ABSTRACT
Aim: The Spontaneously Diabetic Torii (SDT) fatty rat is a novel obese type 2 diabetic model, showing hyperphagia, obesity, and diabetes mellitus from a young age. In this study, we investigated the effects of isolation stress on pathophysiology in SDT fatty rats. Methods: SDT fatty rats (4 weeks old) were housed 3 per cage for 2 weeks and separated as males or females so as each gender will be placed in a separate cage to avoid mating. After acclimatization in 6 weeks of age, the rats were exposed to isolation stress (IS) (one rat per cage, using 5 animals in each sex). In the control group, each sex of experimental rats were housed separately continuously 3 per cage (using 6 animals in each sex). Food intake, body weights, and blood chemical parameters, such as glucose, insulin, triglyceride and total cholesterol levels, of the rats from 6 to 15 weeks of age were measured at every 3 weeks. Satellite groups were prepared for pathological analyses. Necropsy of satellite group was performed at 12 weeks of age, and the pathological analyses, such as adrenal, thymus and spleen, were performed. Results: The blood glucose level in IS group in female SDT fatty rats was significantly increased at 12 weeks of age as compared with that in control group. Female SDT fatty rats showed accelerated diabetic progression, but the male rats did show the effects of IS on the glucose/lipid metabolism. In male SDT fatty rats, an increase of adrenal weight and a decrease of thymus weight were observed in IS group and the female rats in IS group showed a tendency of an increase of adrenal weight and a decrease of thymus weight. In histopathological analyses, adrenal hypertrophy and thymus atrophy were observed in IS group in both male and female rats. Conclusion: Isolation stress affected the progression of diabetes in female SDT fatty rats. Housing conditions is a factor to care for in evaluation of pathophysiology in diabetic models.
ABSTRACT
Aim: Zucker diabetic fatty (ZDF) rat is a type 2 diabetic model with hyperphagia, obesity, and the overt fat storage. The present study investigated effects of food restriction for 15 weeks on the fat distribution in ZDF rats. Methods: ZDF rats were pair-fed with Zucker Lean (ZL) rats from 9 to 24 weeks of age. Body weight and blood chemistry parameters, such as glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acid, were measured every two weeks. The visceral and subcutaneous fat weights were measured at 24 weeks of age by computed tomography (CT) analysis, and the total fat weight and the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) were determined. Results: The ZDF rats showed obesity, hyperglycemia, hyperinsulinemia, and hyperlipidemia as compared with the ZL rats. Pair-fed ZDF rats showed a temporary decrease in body weight and a suppression of hyperglycemia, but the blood insulin and lipid levels increased. Total fat weight was about 2.4 times higher in the ZDF rats than the ZL rats. The total fat weight in Pair-fed ZDF rats was increased by 56%, but the V/S ratio was decreased by 38% at 24 weeks of age. Conclusion: The change of fat distribution by dietary restriction may be related to the improvement of glucose and lipid metabolic disorders in diabetes mellitus with obesity.
ABSTRACT
Aim: The Spontaneously Diabetic Torii (SDT) fatty rat is a metabolic syndrome model, showing obesity, hyperglycemia, dyslipidemia, and hypertension. Moreover, female SDT fatty rats exhibit hepatic steatosis. In this study, metabolic abnormalities, particularly in the liver, were assessed in male SDT fatty rats fed a diet containing 40% fat and 2% cholesterol (HFC-diet). Location and Duration of Study: Niigata University, CLEA Japan and JT Central Pharmaceutical Research Institute, between January and December 2014. Methodology: Male SDT fatty rats in control and HFC groups were fed a standard or HFC-diet (40% fat and 2% cholesterol, based on percentage of total calories) from 5 to 17 weeks of age, respectively. Body weight and blood chemistry parameters were periodically measured and a pathological analysis of the liver was performed at 17 weeks of age. Results: In biological analyses, the HFC group showed increases in body weight, blood insulin, and total cholesterol during the experimental period and an increase in aspartate aminotransferase (AST) at 13 weeks of age. Blood glucose levels in HFC group decreased after 13 weeks of age. In pathological examinations, an increase in liver weight and hepatic steatosis, fatty change and hypertrophy in hepatocyte, were observed in the HFC group. Hepatic steatosis was not observed in the standard-diet group. Conclusion: Male SDT fatty rats fed an HFC-diet may serve as a new nonalcoholic fatty liver disease (NAFLD) model.
ABSTRACT
Aim: This study was conducted to investigate the preventive or therapeutic effect of α- glucosidase inhibitor voglibose in a new model rat, Spontaneously Diabetic Torii-Leprfa (SDT fatty) rat, which is a novel type 2 diabetic rat showing obesity, hyperglycemia and hyperlipidemia from a young age. Place and Duration of Study: Niigata University and JT Central Pharmaceutical Research Institute, between January and August 2011. Methodology: The present study was designed to the preventive and therapeutic effect of voglibose by administering (0.3, 1 mg/kg) voglibose as a dietary admixture to SDT fatty rats from 5 to 11 and 14 to 20 weeks of age, respectively. Results: In the examination of preventive effect, the obtained biochemical results show that voglibose decrease glucose level significantly in dose-dependent manner within 5-11 weeks of age. In voglibose-treated rats at 11 weeks of age, the histopathological pancreatic changes, such as vacuolation and irregular boundaries in islets, were improved. On the other hand, in the examination of therapeutic effect, voglibose improved the hyperglycemia only at a dose of 1 mg/kg within 16-20 weeks of age. Conclusion: Voglibose showed both preventive and therapeutic effects for diabetes in female SDT fatty rats. The SDT fatty rat is a useful model for development of anti-diabetic agents.