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Biomedical subjects

O Tulp

Publications and source records attributed to O Tulp.

8 recordsLinked to original sources
PubMed2004

Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes.

The Streptozotocin (STZ) model of diabetes is commonly used for studies of diabetic nephropathy although the histological lesions of the kidney are mild and do not resemble those seen in diabetic patients. The SHR/N-cp rat model of type II diabetes spontaneously develops pronounced abnormalities in renal histology. In the present study, we compared renal morphology in the STZ rat and the diabetic SHR/N-cp rat. Sprague-Dawley rats received STZ, developed diabetes after 2 days and were treated with insulin. In the SHR/N-cp rat, obesity is inherited as an autosomal recessive trait. The progeny are either lean (used as controls) or obese and diabetic. After 6 months of observation, STZ and SHR/N-cp rats were killed. The renal damage was evaluated by assessing damage indices and by using stereological techniques. In addition, immunohistochemistry and electron microscopy were performed. The glomerular and tubulointerstitial changes were much more pronounced in the diabetic SHR/N-cp compared to the STZ model. In parallel glomerular PCNA+cells were significantly more frequent and expression of TGF-beta and PDGF by immunohistochemistry in glomeruli and in the tubulointerstitial space was more pronounced in SHR/N-cp compared to STZ rats. The glomeruli of SHR/N-cp contained less and larger podocytes as well as smaller mesangial cells embedded in more mesangial matrix compared to STZ. Similarly, less, but larger endothelial cells were found in SHR/N-cp than in STZ rats. The mean glomerular volume was similarly increased in the two models. Albumin excretion was only modestly increased in STZ diabetes, but pronounced in the SHR/N-cp rat. Although the STZ model of diabetes exhibits numerous biochemical sequelae of hyperglycemia, the morphological lesions are unimpressive. In contrast, the diabetic SHR/N-cp exhibits marked structural lesions, particularly podocyte damage and mesangial expansion that promise to make it a more suitable model for investigation of diabetic glomerulosclerosis.

Albuminuria↗
PubMed1998

Localization of leptin receptor immunoreactivity in the lean and obese Zucker rat brain.

Leptin, a product of the obese (ob) gene, is secreted by adipocytes and appears to act as a hormone to regulate food intake, metabolism and body weight. Subcutaneous administration of leptin causes reductions in food intake and body and fat-depot weights in both lean and genetically obese (ob/ob) mice, and leptin infusion into the lateral cerebral ventricles decreases feeding with short latency, suggesting a central site of action. A gene defect in the Zucker obese rat causes an amino acid substitution in the leptin receptor and reduced leptin binding at the cell surface. An antiserum to a portion of the mouse leptin receptor (AA 877-894) located within the intracellular domain was used to label Zucker lean (Fa/?) and obese (fa/fa) rat brain sections. At optimal dilution (1:8000), only cells in the basal forebrain, preoptic area, hypothalamus and brainstem were moderately or intensely labeled. The most intensely-labeled nuclei, the anterior commissural, magnocellular paraventricular, supraoptic, circularis in the anterior hypothalamus and fornical in the lateral hypothalamus contain large neurons that synthesize and secrete vasopressin or oxytocin and their respective neurophysins. Diminished leptin transport into the central nervous system or defective signal transduction in Zucker obese rats may sufficiently compromise leptin regulation of the HPA axis, NPY-immunoreactive neurons or other hypothalamic elements to cause obesity.

Animals↗
PubMed1993

Specific decrease of mitochondrial thermogenic capacity in brown adipose tissue of obese SHR/N-cp rats.

The metabolic properties of brown adipose tissue (BAT), liver, and skeletal muscles were compared in lean and obese diabetic SHR/N-cp rats (a new model of type II diabetes) to test whether the severe insulin resistance of obese animals is specifically associated with a thermogenic defect in BAT. The respiratory response of brown adipocytes to norepinephrine and to agents bypassing the adenylate cyclase complex (dibutyryl cyclic AMP and palmitate) was decreased by two-thirds in obese rats, thereby indicating the presence of a major postreceptor defect. Significantly, total BAT cytochrome oxidase activity, uncoupling protein content, and mitochondrial guanosine 5'-diphosphate binding (3 indexes of BAT thermogenic capacity) were also decreased by two-thirds. The specific activities of these parameters expressed per total BAT mitochondrial protein were not altered either. This indicates that the total number of mitochondria per cell is decreased in BAT of obese rats. In contrast, total tissue cytochrome oxidase activity, protein content, and DNA content all increased by two to three times in the liver of obese SHR/N-cp rats, but these parameters remained unchanged in skeletal muscles (vastus lateralis and soleus). Such a remarkable liver hypertrophy may have occurred as a consequence of the persistent hyperphagia-hyperinsulinemia of obese rats that induced a hyperplasia and/or a hepatocyte polyploidization. This observation together with the fact that daily energy expenditure associated with food intake was markedly increased in obese rats (representing as much as 25% of the total energy expenditure) strongly suggests that the liver plays a major role in energy balance in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗
PubMed1991

Major thermogenic defect associated with insulin resistance in brown adipose tissue of obese diabetic SHR/N-cp rats.

The effects of norepinephrine and insulin on thermogenesis were investigated in adipocytes isolated from brown adipose tissue (BAT) of obese non-diabetic LA/N-cp rats (obese LA), obese diabetic SHR/N-cp rats (obese SHR), and their corresponding lean controls. The maximal calorigenic response (Vmax) and the sensitivity [50% effective concentration (EC50)] to norepinephrine (1 microM) were markedly reduced in brown adipocytes from obese SHR rats compared with their lean controls (3- to 4-fold decrease in the Vmax and 50% increase in the EC50 value). In the same cells, there was a similar decrease in the respiratory response to dibutyryl adenosine 3',5'-cyclic monophosphate, indicating the presence of a major postreceptor defect. Remarkably, total BAT cytochrome oxidase activity (an index of cellular mitochondrial content) was also diminished three to four times in obese SHR rats, suggesting that a reduced BAT mitochondrial content is responsible for the decreased thermogenesis. Ultrastructural studies revealed that the cytoplasm of brown adipocytes from obese SHR rats contained a large lipid droplet, numerous tiny droplets, and few atypical mitochondria with loosely packed cristae. Adipocytes from obese SHR rats were also characterized by a significant resistance to the antithermogenic effect of insulin but not to that of the nonmetabolizable adenosine analogue N6-phenylisopropyl adenosine. In contrast, all the above biochemical parameters were normal in obese LA rats. These results demonstrate that the marked insulin resistance in BAT of obese SHR rats is associated with a decreased responsiveness and sensitivity to norepinephrine, indicating the presence of receptor and postreceptor defects. It is suggested that insulin resistance and/or diabetes in SHR/N-cp rats lead to a decreased mitochondriogenesis in BAT, which results in a reduced thermogenic capacity, thereby contributing to the development of obesity.

Adipose Tissue, Brown↗
PubMed1989

Effects of phenotype, sex, and diet on plasma lipids in LA/N-cp rats.

The LA/N-corpulent (cp) rat is a recently developed congenic strain which exhibits obesity. The effects of phenotype and sex on serum and lipoprotein lipid content were examined in LA/N-cp rats fed either a control or an atherogenic diet high in saturated fat and protein. Obese rats were pair-fed to equivalent lean animals. Results from this study indicate that sex, phenotype, and diet exert significant effects on plasma and lipoprotein cholesterol content. Plasma cholesterol levels were higher in obese compared with lean rats, females than in males, and rats consuming the atherogenic diet compared with the control diet. Plasma and lipoprotein triglyceride levels were significantly increased only in obese compared with lean animals. The increased plasma cholesterol and triglyceride was observed primarily in the chylomicron and very low density lipoprotein fractions. Increased levels of plasma cholesterol were not a result of increased dietary cholesterol absorption or increased liver cholesterol biosynthesis. These data suggest that LA/N-cp rats can serve as a unique rodent model for the study of the interrelationships between hyperlipidemia, obesity, and coronary heart disease.

Animals↗
PubMed1979

Adipose tissue development, growth, and food consumption in protein-malnourished rats.

Effects of protein malnutrition on adipose tissue development were studied in weanling male Sprague-Dawley rats fed isocaloric diets ad libitum containing either 22% (controls) or 8% (protein-malnourished rats) casein, and in rats pair-fed to the protein-malnourished rats with the 22% casein diet. After 32 days on the diet, protein-malnourished rats were 37% and pair-fed 67% the weight of the controls, while torso length was 37% and 73% of controls, respectively. Food consumption relative to body weight was greatest in protein-malnourished rats. Compared to control rats, the distal epididymal adipocyte number in the protein-malnourished rats was decreased in proportion to the decrease in body size and was more closely related to the protein intake than to the total calories consumed. After 32 days on diet, mean adipocyte number per 2 distal pads was 11.7 x 10(6) in controls and 4.3 x 10(6) in protein-malnourished rats. In pair-fed rats, cell number lagged behind controls at 4 and 11 days, but was normal at 32 days (11.4 x 10(6) cells). The distal epididymal pad adipocyte size and percent lipid were similar in all groups during the first 25 days of dietary treatment. Adipocyte size was increased significantly in controls at day 32 compared to the other two groups. At each time studied through day 25 on diet, epididymal pad weight was related to the adipose cell number rather than the cell size. It is concluded that severe restriction of dietary protein during the postweaning period of growth in rats results in decreased epididymal adipocyte proliferation and/or differentiation concomitant with generalized growth retardation, whereas isocaloric feeding of a diet of normal protein content is associated with only a transient delay in adipose tissue development.

Adipose Tissue↗