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Zucker Rats (zucker + rat)
Kinds of Zucker Rats Selected AbstractsProgressive Renal Vascular Proliferation and Injury in Obese Zucker RatsMICROCIRCULATION, Issue 4 2010RADU ILIESCU Microcirculation (2010) 17, 250,258. doi: 10.1111/j.1549-8719.2010.00020.x Abstract Objective:, Obesity, an independent risk factor for chronic kidney disease, may induce renal injury by promoting inflammation. Inflammatory cytokines can induce neovascularization in different organs, including the kidneys. However, whether obesity triggers renal neovascularization and, if so, its effect on renal function has never been investigated. Methods:, Blood pressure, proteinuria, and glomerular filtration rate (GFR) were measured in vivo. Renal microvascular (MV) architecture was studied by 3D micro-CT in lean and obese Zucker rats (LZR and OZR, n = 7/group) at 12, 22, and 32 weeks of age. Renal inflammation was assessed by quantifying interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and ED-1 expression, as renal fibrosis in trichrome-stained cross-sections. Results:, Mild inflammation and lower GFR was only observed in younger OZR, without renal fibrosis or changes in MV density. Interestingly, renal MV density increased in OZR at 32 weeks of age, accompanied by pronounced increase in renal IL-6 and TNF-alpha, ED-1+ cells, proteinuria, decreased GFR, and fibrosis. Conclusions:, This study shows increased renal cortical vascularization in experimental obesity, suggesting neovascularization as an evolving process as obesity progresses. Increased renal vascularization, possibly triggered by inflammation, may reflect an initially compensatory mechanism in obesity. However, increased inflammation and inflammatory-induced neovascularization may further promote renal injury as obesity advances. [source] KATP -mediated Vasodilation is Impaired in Obese Zucker RatsMICROCIRCULATION, Issue 6 2008BENJAMIN L. HODNETT ABSTRACT Objective: Skeletal muscle blood flow during exercise is impaired in obesity. We tested the hypothesis that the attenuated vasodilation in skeletal muscle arterioles of obese Zucker rats (OZR) is due to altered KATP channel-mediated vasodilation. Materials and Methods: KATP channel function was determined in isolated skeletal muscle arterioles in response to the KATP opener cromakalim (0.1,10 , M) during normal myogenic tone and , -adrenergic-mediated tone (0.1 , M phenylephrine). The spinotrapezius muscle was prepared and the vasodilatory responses to muscle stimulation or iloprost (0.028,2.8 , M) were observed before and after the application of the KATP inhibitor, glibenclamide (10 , M). Channel subunit expression was determined by using western blot analyses. Results: Cromakalim concentration-response curves were shifted in OZR as compared to lean controls. OZR exhibited impaired functional and iloprost-induced vasodilation as compared to the lean controls. Glibenclamide inhibited the functional and iloprost-induced dilation in the lean rats with no effects in the obese animals. Channel subunit expression was similar in femoral arteries. Conclusion:The impaired functional vasodilation in the OZR is associated with altered KATP channel sensitivity. [source] Effects of cevoglitazar, a dual PPAR,/, agonist, on ectopic fat deposition in fatty Zucker ratsDIABETES OBESITY & METABOLISM, Issue 6 2009D. Laurent Aim:, By acting as both insulin sensitizers and lipid-lowering agents, dual-acting peroxisome proliferator-activated receptors ,/, (PPAR,/,) agonists may be used to improve glucose tolerance in type 2 diabetic patients without inducing adiposity and body weight gain. Here, in an animal model of obesity and insulin resistance, the metabolic response to cevoglitazar, a dual PPAR,/,, was characterized using a combination of in vivo and ex vivo magnetic resonance methodologies and compared to treatment effects of fenofibrate, a PPAR, agonist, and pioglitazone, a PPAR, agonist. Methods:, Four groups of fatty Zucker rats: (i) Vehicle; (ii) fenofibrate 150 mg/kg; (iii) pioglitazone 30 mg/kg; and (iv) cevoglitazar 5 mg/kg were investigated before and after treatment. Animals were fed a fat-enriched (54% kcal fat) diet for 6 weeks, 2 weeks high of fat,exposure alone followed by a 4-week dosing period. Results and conclusions:, Cevoglitazar was as effective as pioglitazone at improving glucose tolerance. However, unlike pioglitazone, both fenofibrate and cevoglitazar reduced BW gain and adiposity, independent of food intake. All three treatment regimens normalized intramyocellular lipids. Metabolic profiling showed that in the muscle cevoglitazar improves the lipid profile via both PPAR,- and PPAR,-mediated mechanisms. Pioglitazone reduced hepatic lipid accumulation, while cevoglitazar and fenofibrate reduced hepatic lipid concentration below baseline levels (p < 0.05). Metabolic profiling showed that in the liver, cevoglitazar functions largely through PPAR, agonism resulting in increased ,-oxidation. Cevoglitazar only induced small changes to the lipid composition of visceral fat. In subcutaneous fat, however, cevoglitazar induced changes similar to those observed with fenofibrate suggesting export of fatty acids from this depot. [source] Leptin-mediated neovascularization is a prerequisite for progression of nonalcoholic steatohepatitis in rats,HEPATOLOGY, Issue 4 2006Mitsuteru Kitade Nonalcoholic steatohepatitis (NASH) may cause fibrosis, cirrhosis, and hepatocellular carcinoma (HCC); however, the exact mechanism of disease progression is not fully understood. Angiogenesis has been shown to play an important role in the progression of chronic liver disease. The aim of this study was to elucidate the role of angiogenesis in the development of liver fibrosis and hepatocarcinogenesis in NASH. Zucker rats, which naturally develop leptin receptor mutations, and their lean littermate rats were fed a choline-deficient, amino acid,defined diet. Both Zucker and littermate rats showed marked steatohepatitis and elevation of oxidative stress markers (e.g., thiobarbital acid reactive substances and 8-hydroxydeoxyguanosine). In sharp contrast, liver fibrosis, glutathione- S -transferase placental form (GST-P)-positive preneoplastic lesions, and HCC developed in littermate rats but not in Zucker rats. Hepatic neovascularization and the expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, only increased in littermate rats, almost in parallel with fibrogenesis and carcinogenesis. The CD31-immunopositive neovessels were mainly localized either along the fibrotic septa or in the GST-P,positive lesions. Our in vitro study revealed that leptin exerted a proangiogenic activity in the presence of VEGF. In conclusion, these results suggest that leptin-mediated neovascularization coordinated with VEGF plays an important role in the development of liver fibrosis and hepatocarcinogenesis in NASH. (HEPATOLOGY 2006;44:983,991.) [source] Effects of microcrystalline plant sterol suspension and a powdered plant sterol supplement on hypercholesterolemia in genetically obese Zucker ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2003Jari Summanen ABSTRACT Because dietary fat appears to be an effective vehicle for dispensing plant sterols into the diet, a special plant-sterol-containing ingredient has recently been developed. This ingredient is a plant sterol suspension in oil in which the sterols are in microcrystalline form. The objective of the present study was to analyse the cholesterol-lowering effects and safety of two different plant sterol preparations, an orally administered microcrystalline plant sterol suspension (MPS) in rapeseed oil and a powdered plant sterol supplement, in obese Zucker rats. Dietary plant sterol supplements (0.5%, w/w) were given concurrently with a high cholesterol diet (HCD, 1% cholesterol and 18% fat, w/w). No significant changes in serum triglyceride, blood glucose, serum glutamate oxaloacetic transaminase and glutamic pyruvic transaminase values or body and liver weights were observed. The powdered plant sterol supplement lowered the serum cholesterol by 25% (P< 0.05) and the MPS diet by 35% (P< 0.001) compared with HCD by the end of the 12-week experiment. Interestingly, the plant sterol supplements also produced a marked reduction in serum ubiquinone levels, suggesting a possible effect on isoprene synthesis. Unlike the powdered plant sterol, both MPS and plain rape-seed oil decreased the serum baseline diene conjugation values, suggesting that they protect against oxidative stress-induced lipid peroxidation in rats. This lipid peroxidation diminishing effect is probably due to some antioxidative components in rapeseed oil. These findings indicate that an unesterified plant sterol, such as the microcrystalline suspension in oil, effectively prevents cholesterol absorption in obese Zucker rats. [source] Hydrophilic interaction and reversed-phase ultra-performance liquid chromatography TOF-MS for metabonomic analysis of Zucker rat urineJOURNAL OF SEPARATION SCIENCE, JSS, Issue 9 2008Helen G. Gika Abstract Hydrophilic interaction chromatography (HILIC) provides a complementary technique to RP methods for the retention of polar analytes for LC-MS-based metabonomic studies. Combining the advantages of both RP and HILIC separations with the efficient and rapid separations obtained using sub-2 ,m particles via the recently introduced ultra-performance LC (UPLC) enables increased coverage of the metabolites present in biological samples to be achieved. Here an HILIC-UPLC-MS method was developed to provide metabolite profiles for urine samples obtained from male Zucker rats. The resulting data were compared with results obtained for the same samples by RP-UPLC-MS and demonstrated the complementary nature of the two separations with both methods enabling discrimination between the different sample types. Interestingly sample type differentiation was based on different markers. [source] Progressive Renal Vascular Proliferation and Injury in Obese Zucker RatsMICROCIRCULATION, Issue 4 2010RADU ILIESCU Microcirculation (2010) 17, 250,258. doi: 10.1111/j.1549-8719.2010.00020.x Abstract Objective:, Obesity, an independent risk factor for chronic kidney disease, may induce renal injury by promoting inflammation. Inflammatory cytokines can induce neovascularization in different organs, including the kidneys. However, whether obesity triggers renal neovascularization and, if so, its effect on renal function has never been investigated. Methods:, Blood pressure, proteinuria, and glomerular filtration rate (GFR) were measured in vivo. Renal microvascular (MV) architecture was studied by 3D micro-CT in lean and obese Zucker rats (LZR and OZR, n = 7/group) at 12, 22, and 32 weeks of age. Renal inflammation was assessed by quantifying interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and ED-1 expression, as renal fibrosis in trichrome-stained cross-sections. Results:, Mild inflammation and lower GFR was only observed in younger OZR, without renal fibrosis or changes in MV density. Interestingly, renal MV density increased in OZR at 32 weeks of age, accompanied by pronounced increase in renal IL-6 and TNF-alpha, ED-1+ cells, proteinuria, decreased GFR, and fibrosis. Conclusions:, This study shows increased renal cortical vascularization in experimental obesity, suggesting neovascularization as an evolving process as obesity progresses. Increased renal vascularization, possibly triggered by inflammation, may reflect an initially compensatory mechanism in obesity. However, increased inflammation and inflammatory-induced neovascularization may further promote renal injury as obesity advances. [source] KATP -mediated Vasodilation is Impaired in Obese Zucker RatsMICROCIRCULATION, Issue 6 2008BENJAMIN L. HODNETT ABSTRACT Objective: Skeletal muscle blood flow during exercise is impaired in obesity. We tested the hypothesis that the attenuated vasodilation in skeletal muscle arterioles of obese Zucker rats (OZR) is due to altered KATP channel-mediated vasodilation. Materials and Methods: KATP channel function was determined in isolated skeletal muscle arterioles in response to the KATP opener cromakalim (0.1,10 , M) during normal myogenic tone and , -adrenergic-mediated tone (0.1 , M phenylephrine). The spinotrapezius muscle was prepared and the vasodilatory responses to muscle stimulation or iloprost (0.028,2.8 , M) were observed before and after the application of the KATP inhibitor, glibenclamide (10 , M). Channel subunit expression was determined by using western blot analyses. Results: Cromakalim concentration-response curves were shifted in OZR as compared to lean controls. OZR exhibited impaired functional and iloprost-induced vasodilation as compared to the lean controls. Glibenclamide inhibited the functional and iloprost-induced dilation in the lean rats with no effects in the obese animals. Channel subunit expression was similar in femoral arteries. Conclusion:The impaired functional vasodilation in the OZR is associated with altered KATP channel sensitivity. [source] Administration of Cyperus rotundus tubers extract prevents weight gain in obese Zucker ratsPHYTOTHERAPY RESEARCH, Issue 8 2007Bernard Lemaure Abstract Cyperus rotundus L. (Cyperaceae; C. rotundus) is an Indian medicinal plant demonstrated to exert multiple health benefits. The purpose of the present study was to test the biological efficacy of C. rotundus tubers extract on weight control in obese Zucker rats. It was demonstrated that administration of 45 or 220 mg/kg/day of C. rotundus tubers hexane extract for 60 days in Zucker rats induced a significant reduction in weight gain without affecting food consumption or inducing toxicity. In vitro, 250 µg/mL of this extract was able to stimulate lipolysis in 3T3-F442 adipocytes suggesting that this medicinal plant contains activators of , -adrenoreceptors (AR). The binding assay performed on the rat ,3-AR isoform, known to induce thermogenesis, demonstrated that C. rotundus tubers extract can consistently and effectively bind to this receptor. These data suggest that the effect on weight gain exerted by C. rotundus tubers extract may be mediated, at least partially, through the activation of the ,3-AR. In conclusion, C. rotundus tubers extract prove to be a new herbal supplement for controlling body weight preferentially in ,3-AR sensitive species. Copyright © 2007 John Wiley & Sons, Ltd. [source] The detection of phenotypic differences in the metabolic plasma profile of three strains of Zucker rats at 20 weeks of age using ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2006Robert S. Plumb Analysis of biological fluids using ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) (metabonomics) can allow new insights to be gained into disease processes, with advances in chromatographic techniques enabling the detection of thousands of metabolites. In this work metabonomics has been used to investigate the metabolic processes involved in type II diabetes in the Zucker obese rat. Plasma was analyzed from three different strains, the Zucker (fa/fa) obese, Zucker lean and the lean/(fa) obese cross. Using UPLC/MS, ca. 10,000 ions were detected due to the narrow peak widths and excellent peak shapes achieved with this technology. Confidence in the chromatographic performance was demonstrated by the use of quality control standards. The positive and negative ion total ion chromatograms obtained from the three strains were readily distinguishable using multivariate statistical analysis. The greatest difference was observed between the Zucker lean and Zucker lean/(fa) rats compared to the Zucker (fa/fa) obese rats. Positive ions m/z 220 (4.36,min), 282(3.78,min), 359 (5.33,min) and 405 (7.77,min) were elevated in the plasma derived from Zucker lean rats whilst ions m/z 385 (6.80,min) and 646 (4.36,min) were at a lower concentration compared to the plasma from the Zucker (fa/fa) obese animals. Negative ions elevated in the Zucker lean rats included m/z 212 (2.30,min), 514 (2.85,min), 295 (4.39,min), 329 (3.11,min), 343 (2.86,min) and 512 (2.86,min) with ions m/z 538 (4.18,min), 568 (4.18,min), 568 (5.09,min) and 612 (4.30,min) being raised in the samples derived from Zucker (fa/fa) obese animals. The ion m/z 514 (3.85,min) was found to correspond to taurocholate, providing further support for an involvement of taurine metabolism in diabetes. Copyright © 2006 John Wiley & Sons, Ltd. [source] Therapeutic Targets in Liver Transplantation: Angiotensin II in Nonsteatotic Grafts and Angiotensin-(1,7) in Steatotic GraftsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009I. Alfany-Fernandez Numerous steatotic livers are discarded as unsuitable for transplantation because of their poor tolerance of ischemia-reperfusion(I/R). The injurious effects of angiotensin (Ang)-II and the benefits of Ang-(1,7) in various pathologies are well documented. We examined the generation of Ang II and Ang-(1,7) in steatotic and nonsteatotic liver grafts from Zucker rats following transplantation. We also studied in both liver grafts the effects of Ang-II receptors antagonists and Ang-(1,7) receptor antagonists on hepatic I/R damage associated with transplantation. Nonsteatotic grafts showed higher Ang II levels than steatotic grafts, whereas steatotic grafts showed higher Ang-(1,7) levels than nonsteatotic grafts. Ang II receptor antagonists protected only nonsteatotic grafts against damage, whereas Ang-(1,7) receptor antagonists were effective only in steatotic grafts. The protection conferred by Ang II receptor antagonists in nonsteatotic grafts was associated with ERK 1/2 overexpression, whereas the beneficial effects of Ang-(1,7) receptor antagonists in steatotic grafts may be mediated by NO inhibition. Our results show that Ang II receptor antagonists are effective only in nonsteatotic liver transplantation and point to a novel therapeutic target in liver transplantation based on Ang-(1,7), which is specific for steatotic liver grafts. [source] INCREASED SYSTEMIC OXIDATIVE AND NITRATIVE STRESS IN A NEW CONGENIC MODEL OF METABOLIC SYNDROME DERIVED FROM STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND ZUCKER FATTY RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2007Yu Yamaguchi SUMMARY 1Oxidative stress has been recognized as an important factor in the biology of lifestyle-related diseases. Systemic oxidative stress may increase in metabolic syndrome characterized by a cluster of metabolic risk factors. To confirm this hypothesis, we investigated systemic oxidative/nitrative stress in a new congenic model of metabolic syndrome, namely SHRSP/ZF rats, which are derived from stroke-prone spontaneously hypertensive (SHRSP) and Zucker fatty (Zucker) rats. 2The SHRSP/ZF rats display obesity, hypertension, hyperlipidaemia, hyperglycaemia and glucose intolerance. At 6 weeks of age, SHRSP/ZF rats already showed increases in serum levels of thiobarbituric acid-reactive substances (TBARS) and oxidatively modified low-density lipoprotein (Ox-LDL) compared with lean SHRSP littermates and Zucker rats, whereas serum levels of 8-hydroxy-2,-deoxyguanine (8-OHdG), 3-nitrotyrosine, 3-chlorotyrosine and high-sensitivity C-reactive protein (hsCRP), an inflammatory marker, did not differ significantly among the three rat strains. However, levels of these oxidative/nirative stress markers in SHRSP/ZF rats, as well as in SHRSP, increased gradually with age. After 36 weeks of age, the levels of TBARS, 8-OHdG, 3-nitrotyrosine and hsCRP in SHRSP/ZF rats increased rapidly and three of six rats died thereafter. Increased oxidative/nitrative stress may be associated with death in these rats. 3Our findings indicate that systemic oxidative/nitrative stress is evidently increased in metabolic syndrome. [source] | |||||||||||||