scholarly journals Obesity and Age-Related Changes in the Brain of the Zucker Lepr fa/fa Rats

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1356 ◽  
Author(s):  
Daniele Tomassoni ◽  
Ilenia Martinelli ◽  
Michele Moruzzi ◽  
Maria Vittoria Micioni Di Bonaventura ◽  
Carlo Cifani ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Body Weight Gain ◽  
Zucker Rats ◽  
Transporter Protein ◽  
Age Related ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Immunohistochemical Techniques ◽  
The Brain ◽  
Cognitive Alterations

Metabolic syndrome (MetS) is an association between obesity, dyslipidemia, hyperglycemia, hypertension, and insulin resistance. A relationship between MetS and vascular dementia was hypothesized. The purpose of this work is to investigate brain microanatomy alterations in obese Zucker rats (OZRs), as a model of MetS, compared to their counterparts lean Zucker rats (LZRs). 12-, 16-, and 20-weeks-old male OZRs and LZRs were studied. General physiological parameters and blood values were measured. Immunochemical and immunohistochemical techniques were applied to analyze the brain alterations. The morphology of nerve cells and axons, astrocytes and microglia were investigated. The blood–brain barrier (BBB) changes occurring in OZRs were assessed as well using aquaporin-4 (AQP4) and glucose transporter protein-1 (GLUT1) as markers. Body weight gain, hypertension, hyperglycemia, and hyperlipidemia were found in OZRs compared to LZRs. In the frontal cortex and hippocampus, a decrease of neurons was noticeable in the older obese rats in comparison to their age-matched lean counterparts. In OZRs, a reduction of neurofilament immunoreaction and gliosis was observed. The BBB of older OZRs revealed an increased expression of AQP4 likely related to the development of edema. A down-regulation of GLUT1 was found in OZRs of 12 weeks of age, whereas it increased in older OZRs. The behavioral analysis revealed cognitive alterations in 20-week-old OZRs. Based on these results, the OZRs may be useful for understanding the mechanisms through which obesity and related metabolic alterations induce neurodegeneration.

Relationship of adipocyte size to hyperphagia in developing male obese Zucker rats

1992 ◽  
Vol 262 (1) ◽  
pp. R33-R38 ◽  
Author(s):  
J. R. Vasselli ◽  
J. A. Fiene ◽  
C. A. Maggio
Keyword(s):  
Adipose Tissue ◽  
Body Weight Gain ◽  
Zucker Rats ◽  
Lipoprotein Lipase Activity ◽  
Adipocyte Size ◽  
High Fat ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Relationship Of ◽  
Cumulative Intake

In growing male obese Zucker rats, hyperphagia reaches a maximum or “breakpoint” and declines at an earlier age with high fat than with chow-type diets. A serial adipose tissue biopsy technique was used to correlate changes of retroperitoneal adipocyte size and feeding behavior in 5- to 7-wk-old male lean and obese rats fed laboratory chow or a 35% fat diet until 30 wk of age. Although chow-fed groups had significantly greater cumulative intake, fat-fed groups had significantly greater body weight gain, retroperitoneal depot weight, and adipocyte number. Mean adipocyte size increased continuously in chow-fed groups but decreased over weeks 20-30 in fat-fed groups, reflecting increased adipocyte number. In fat-fed obese rats, hyperphagia reached a breakpoint at 11 wk and disappeared by 13 wk. In chow-fed obese rats, hyperphagia reached a breakpoint at 15-16 wk and disappeared by 19 wk. Biopsy samples revealed that adipocyte size of fat-fed obese rats was already close to maximal at 10 wk (1.12 micrograms lipid), while that of chow-fed obese rats only approached maximal at 20 wk (0.81 microgram lipid). At these time points, lipoprotein lipase activity paralleled adipocyte size. These data indicate that the duration of the growing obese rat's hyperphagia coincides with adipocyte filling and suggest the existence of feeding stimulatory and inhibitory signals from adipose tissue.

scholarly journals Failure of insulin-regulated recruitment of the glucose transporter GLUT4 in cardiac muscle of obese Zucker rats is associated with alterations of small-molecular-mass GTP-binding proteins

1995 ◽  
Vol 311 (1) ◽  
pp. 161-166 ◽  
Author(s):  
I Uphues ◽  
T Kolter ◽  
B Goud ◽  
J Eckel
Keyword(s):  
Plasma Membranes ◽  
Microsomal Fraction ◽  
Glucose Transporter ◽  
Zucker Rats ◽  
Gtp Binding Protein ◽  
Insulin Resistant ◽  
Gtp Binding ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Glucose Transporter Glut4

Cardiac ventricular tissue of lean and genetically obese (fa/fa) Zucker rats was used to study the expression, subcellular distribution and insulin-induced recruitment of the glucose transporter GLUT4 and to elucidate possible molecular alterations of the translocation process. Hearts were removed from basal and insulin-treated (20 min) lean and obese Zucker rats, and processed for subcellular fractionation and Western blotting of proteins. In obese rats, the total GLUT4 content in a crude membrane fraction was reduced to 75 +/- 8% (P = 0.019) of lean controls. In contrast, GLUT4 abundance in plasma membranes was not significantly different between lean and obese rats with a concomitant decrease (47 +/- 3%) in the microsomal fraction of obese animals. In plasma membranes of lean animals insulin was found to increase the GLUT4 abundance to 294 +/- 43% of control with a significantly (P = 0.009) reduced effect in the obese group (139 +/- 10% of control). In these animals insulin failed to recruit GLUT4 from the microsomal fraction, whereas the hormone induced a significant decrease (41 +/- 4%) of microsomal GLUT4 in lean controls. In GLUT4-enriched membrane vesicles, obtained from cardiac microsomes of lean rats, a 24 kDa GTP-binding protein could be detected, whereas no significant labelling of this species was observed in GLUT4 vesicles prepared from obese animals. In addition to the translocation of GLUT4, insulin was found to promote the movement of the small GTP-binding protein rab4A from the cytosol (decrease to 61 +/- 13% of control) to the plasma membrane (increase to 177 +/- 19% of control) in lean rats with no effect of the hormone on rab4A redistribution in the obese group. In conclusion, cardiac glucose uptake of insulin-resistant obese Zucker rats is subject to multiple cellular abnormalities involving a reduced expression, altered redistribution and defective recruitment of GLUT4. We show here an association of the latter defect with alterations at the level of small GTP-binding proteins possibly leading to an impaired trafficking of GLUT4 in the insulin-resistant state.

scholarly journals Increased gene expression of lipogenic enzymes and glucose transporter in white adipose tissue of suckling and weaned obese Zucker rats

1991 ◽  
Vol 279 (1) ◽  
pp. 303-308 ◽  
Author(s):  
L Pénicaud ◽  
P Ferré ◽  
F Assimacopoulos-Jeannet ◽  
D Perdereau ◽  
A Leturque ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Glucose Transporter ◽  
Zucker Rats ◽  
Lipogenic Enzymes ◽  
Glut 4 ◽  
Obese Rats ◽  
Before And After ◽  
Plasma Insulin Levels ◽  
Obese Zucker Rats

Previous experiments have shown that insulin-induced glucose utilization is increased in white adipose tissue of young obese Zucker rats. We have investigated the possible role of over-expression of the muscle/fat glucose transporter (Glut 4) and key lipogenic enzymes in this increased insulin-responsiveness. The amount or activity and the mRNA concentrations of Glut 4, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were measured before and after weaning in white adipose tissue of obese and lean Zucker rats. Comparison of the levels of Glut 4 and lipogenic-enzyme expression in 15-day-old suckling and 30-day-old weaned rats on a high-carbohydrate diet shows a marked increase in the latter group. The increase was, in lean and obese rats respectively, 6- and 7-fold for the amount of Glut 4 and 2- and 3-fold for its mRNA concentrations, 40- and 100-fold for the activity of lipogenic enzymes (FAS and ACC) and 30- and 10-fold for their mRNA concentrations. Furthermore, all these parameters, except the amount of Glut 4, were 2-5-fold higher in obese rats, both before and after weaning. Changes at weaning were largely blunted when rats were weaned on to a high-fat diet, although the differences between lean and obese rats persisted, and even became significant for the amount of Glut 4. Whatever the experimental conditions, plasma insulin levels were significantly higher in obese than in lean rats. These results indicate the existence of an enhanced expression of Glut 4, FAS and ACC in white adipose tissue of young obese fa/fa rats which could be related to the increased plasma insulin levels.

Insulin sensitizer YM268 ameliorates insulin resistance by normalizing the decreased content of GLUT4 in adipose tissue of obese Zucker rats

1997 ◽  
pp. 693-700 ◽  
Author(s):  
A Shimaya ◽  
O Noshiro ◽  
R Hirayama ◽  
T Yoneta ◽  
K Niigata ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Transporter ◽  
Zucker Rats ◽  
Epididymal Adipose Tissue ◽  
Maximum Effect ◽  
Insulin Sensitizer ◽  
Peripheral Insulin Resistance ◽  
Obese Rats ◽  
Obese Zucker Rats

Genetically obese Zucker rats exhibit mild hyperglycaemia and hyperinsulinaemia suggesting the existence of peripheral insulin resistance. We have examined the effects of YM268, an analogue of thiazolidinedione, on the content and translocation of a glucose transporter (GLUT4) in epididymal adipose tissue in 11-week-old obese and lean Zucker rats. The administration of YM268 at a dose of 10 mg/kg for 2 weeks ameliorated hyperglycaemia, hyperinsulinaemia, and impaired glucose tolerance after glucose load in obese rats. The GLUT4 content per fat pad in obese rats was reduced to 36% of that in lean littermates. Obese rats treated with YM268 increased GLUT4 concentrations in their fat pads from a basal value of 36% up to 191% of the level in lean rats. Furthermore, in adipocytes prepared from obese rats, an increase in the ratio of GLUT4 in plasma membrane to the total amount of GLUT4 (PM-GLUT4 ratio) induced by the submaximal concentration of insulin (0.3 nmol/l) was significantly attenuated compared with that in lean rats. But the maximum effect of insulin (3 nmol/l) was not attenuated. Meanwhile, YM268 had no significant effect on the attenuated PM-GLUT4 ratio in response to insulin in obese rats. These data suggested that one of the mechanisms by which YM268 improved insulin resistance in obese Zucker rats was to normalize the decreased GLUT4 content in the adipose tissue.

Effect of somatotropin and feed restriction on body composition and adipose metabolism in obese Zucker rats

1995 ◽  
Vol 269 (1) ◽  
pp. E137-E144 ◽  
Author(s):  
M. J. Azain ◽  
D. B. Hausman ◽  
T. R. Kasser ◽  
R. J. Martin
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Zucker Rats ◽  
Feed Restriction ◽  
Reduced Body ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Isolated Adipocytes ◽  
Obese Zucker Rats ◽  
Lean Group

The objective of the present study was to determine whether exogenous somatotropin (STH) administration in conjunction with feed restriction could alter the composition of gain in the obese rat. Five-week-old female lean and obese Zucker rats were assigned to the following treatments for 6 wk: ad libitum fed (AL), restricted (approximately 75% of AL lean), and restricted with STH (2 mg STH/day). Growth rate was decreased in restricted groups and was normalized to that of the AL lean group in restricted rats treated with STH. In lean rats, restriction decreased protein accretion. Restriction plus STH treatment decreased lipid accretion but increased protein accretion and body weight gain compared with the AL lean group. As expected, feed restriction reduced body size in obese rats, but carcass lipid was maintained at 44%, a level similar to that of the AL obese rats. Lipid accretion rate was decreased with restriction in obese rats and was further reduced, to a level similar to that of the lean group, in the obese rats that were restricted and treated with STH. Protein accretion was decreased in the restricted obese group but was normalized in those treated with STH to a level similar to that in the AL lean group. Basal rates of lipolysis in isolated adipocytes were not affected by STH. However, STH treatment normalized the responsiveness of cells from the obese rats to stimulation of lipolysis by isoproterenol. The results demonstrate that a combination of caloric restriction and STH was effective in normalizing body weight and composition of gain in the obese Zucker rat.

Scapular brown fat removal enhances development of adiposity in cold-exposed obese Zucker rats

1984 ◽  
Vol 247 (5) ◽  
pp. R918-R926 ◽  
Author(s):  
J. S. Stern ◽  
T. Inokuchi ◽  
T. W. Castonguay ◽  
S. J. Wickler ◽  
B. A. Horwitz
Keyword(s):  
Body Composition ◽  
Weight Gain ◽  
Citrate Synthase ◽  
Body Weight Gain ◽  
Cell Number ◽  
Brown Fat ◽  
Zucker Rats ◽  
Obese Rats ◽  
Fat Removal ◽  
Obese Zucker Rats

To investigate the contribution of brown fat (BAT) to the development of obesity in genetically obese Zucker rats (fa/fa), scapular brown fat (SBAT) was removed from obese and lean 4-wk-old females. Eight weeks after surgery there was no regrowth of SBAT. Lipectomy had no effect on body weight gain, food intake, and body composition when rats were housed at 25 degrees C. Lean rats completely compensated for the lipectomy by increasing BAT mass, protein, cellularity, and activity of citrate synthase (CS) in axillary, perirenal, and thoracic depots. beta-Hydroxyacyl-coenzyme A dehydrogenase (HOAD) activity was increased, but compensation was incomplete. In lipectomized obese rats, only BAT protein and cell number were increased sufficiently for complete compensation. In a second experiment SBAT was removed from obese and lean rats, but rats were housed in the cold (10 degrees C) for 8 wk. In lean rats, although compensation was incomplete, it was sufficient to maintain a weight gain and body composition comparable with sham-operated lean rats. In obese rats, where there was little or no compensation for lipectomy, weight gain and fat deposition were greater than observed in sham-operated obese controls. These data support the hypothesis that reducing the amount of functional BAT contributes to the development of increased adiposity.

scholarly journals Chronic suppression of insulin by diazoxide alters the activities of key enzymes regulating hepatic gluconeogenesis in Zucker rats

2002 ◽  
pp. 871-879 ◽  
Author(s):  
R Alemzadeh ◽  
S Holshouser ◽  
P Massey ◽  
J Koontz
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Zucker Rats ◽  
Hepatic Glycogen ◽  
Hepatic Gluconeogenesis ◽  
Key Enzymes ◽  
Glucose Transporter 2 ◽  
Obese Rats ◽  
Obese Zucker Rats

OBJECTIVES: Chronic attenuation of hyperinsulinemia by diazoxide (DZ), an inhibitor of glucose-mediated insulin secretion, improved insulin sensitivity and glucose tolerance and caused down-regulation of lipid metabolizing enzymes in adipose tissue and decreased the rate of weight gain in mildly hyperglycemic obese Zucker rats. Since the liver plays a central role in glucose homeostasis, we studied the effect of chronic insulin suppression on key insulin-sensitive enzymes regulating hepatic gluconeogenesis. METHODS: DZ (150 mg/kg per day) or vehicle (control) was administered to 7-week-old female obese and lean Zucker rats for a period of 4 weeks. RESULTS: DZ-treated animals showed lower fasting plasma insulin levels (P<0.001) than their controls. Plasma glucose levels were lower in DZ obese rats than in controls (P<0.001), without a significant change in DZ lean animals. DZ had no effect on glucose transporter 2 protein expression in either strain. DZ treatment resulted in lower hepatic glucokinase (P<0.001) and glucose-6-phosphatase (P<0.0001) and phosphoenolpyruvate carboxykinase (PEPCK) activities only in obese rats compared with controls (P<0.001). However, DZ-treated lean rats demonstrated higher PEPCK activity than controls (P<0.002). DZ-treated animals demonstrated enhanced hepatic glucose-6-phosphate content (P<0.01), glycogen synthase activity (P<0.0001) and glycogen content (P<0.02) compared with their controls despite increased hepatic glycogen phosphorylase a activity in these animals (P<0.02). CONCLUSIONS: Chronic suppression of hyperinsulinemia in obese Zucker rats by DZ decreased the activities of key enzymes regulating hepatic gluconeogenesis, implying that attenuation of the hyperinsulinemic state by DZ may be therapeutically beneficial.

scholarly journals High Na intake increases renal angiotensin II levels and reduces expression of the ACE2-AT2R-MasR axis in obese Zucker rats

2012 ◽  
Vol 303 (3) ◽  
pp. F412-F419 ◽  
Author(s):  
Preethi Samuel ◽  
Quaisar Ali ◽  
Rifat Sabuhi ◽  
Yonnie Wu ◽  
Tahir Hussain
Keyword(s):  
Sodium Intake ◽  
Zucker Rats ◽  
Kidney Cortex ◽  
Complex Nature ◽  
Ang Ii ◽  
Pronounced Increase ◽  
High Sodium ◽  
High Sodium Intake ◽  
Obese Rats ◽  
Obese Zucker Rats

High sodium intake is known to regulate the renal renin-angiotensin system (RAS) and is a risk factor for the pathogenesis of obesity-related hypertension. The complex nature of the RAS reveals that its various components may have opposing effects on natriuresis and blood pressure regulation. We hypothesized that high sodium intake differentially regulates and shifts a balance between opposing components of the renal RAS, namely, angiotensin-converting enzyme (ACE)-ANG II-type 1 ANG II receptor (AT1R) vs. AT2-ACE2-angiotensinogen (Ang) (1–7)-Mas receptor (MasR), in obesity. In the present study, we evaluated protein and/or mRNA expression of angiotensinogen, renin, AT1A/BR, ACE, AT2R, ACE2, and MasR in the kidney cortex following 2 wk of a 8% high-sodium (HS) diet in lean and obese Zucker rats. The expression data showed that the relative expression pattern of ACE and AT1BR increased, renin decreased, and ACE2, AT2R, and MasR remained unaltered in HS-fed lean rats. On the other hand, HS intake in obese rats caused an increase in the cortical expression of ACE, a decrease in ACE2, AT2R, and MasR, and no changes in renin and AT1R. The cortical levels of ANG II increased by threefold in obese rats on HS compared with obese rats on normal salt (NS), which was not different than in lean rats. The HS intake elevated mean arterial pressure in obese rats (27 mmHg) more than in lean rats (16 mmHg). This study suggests that HS intake causes a pronounced increase in ANG II levels and a reduction in the expression of the ACE2-AT2R-MasR axis in the kidney cortex of obese rats. We conclude that such changes may lead to the potentially unopposed function of AT1R, with its various cellular and physiological roles, including the contribution to the pathogenesis of obesity-related hypertension.

scholarly journals Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats

2005 ◽  
Vol 153 (6) ◽  
pp. 963-969 ◽  
Author(s):  
Dorte X Gram ◽  
Anker J Hansen ◽  
Michael Wilken ◽  
Torben Elm ◽  
Ove Svendsen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Sensory Nerve ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Nerve Activity ◽  
Calcitonin Gene ◽  
Obese Rats ◽  
Obese Zucker Rats

Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity – and therefore might be involved in the pathophysiology – is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this. Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age) would also ameliorate glycaemia in this non-diabetic model, we assessed oral glucose tolerance at 7 weeks after capsaicin. Results: It was found that plasma CGRP levels were elevated in obese Zucker rats prior to the onset of obesity (16.1±3.4 pmol/l in pre-obese Zucker rats vs 6.9±1.1 pmol/l in lean littermates; P = 0.015) despite similar body weights. Furthermore, capsaicin desensitization reduced both fasting blood glucose (4.3±0.2 mmol/l vs 5.1±0.2 mmol/l in controls; P = 0.050) as well as the mean blood glucose level during an oral glucose tolerance test (OGTT) (6.8±0.3 mmol/l vs 8.6±0.5 mmol/l in control obese rats; P = 0.024) whereas the plasma insulin levels during the OGTT were unchanged. However this did not lead to an improvement in insulin resistance or to a reduction of tissue triglyceride accumulation in muscle or liver. Conclusion: We concluded that capsaicin-induced sensory nerve desensitization improves glucose tolerance in Zucker rats. Since, in this study, plasma CGRP levels, a marker of sensory nerve activity, were increased in the pre-obese rats, our data support the hypothesis that increased activity of sensory nerves precedes the development of obesity and insulin resistance in Zucker rats.

scholarly journals Adipose-tissue-specific increase in glyceraldehyde-3-phosphate dehydrogenase activity and mRNA amounts in suckling pre-obese Zucker rats. Effect of weaning

1988 ◽  
Vol 254 (2) ◽  
pp. 483-487 ◽  
Author(s):  
I Dugail ◽  
A Quignard-Boulange ◽  
R Bazin ◽  
X Le Liepvre ◽  
M Lavau
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Zucker Rats ◽  
Tissue Specific ◽  
Gapdh Gene ◽  
Gapdh Activity ◽  
Weanling Rats ◽  
Obese Rats ◽  
Specific Increase ◽  
Obese Zucker Rats

The regulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression was studied during the onset of obesity in the genetically obese (fa/fa) rat by determination of GAPDH activity and hybridizable mRNA amounts in adipose tissue and liver from suckling and weanling rats. GADPH activity remained low throughout the suckling period, and a burst of activity occurred after weaning in both lean and obese pups. As early as 7 days of age, adipose tissue from pre-obese rats displayed a significant increase in enzyme activity, whereas no difference could be detected in the liver. In both suckling (16 days of age) and weanling (30 days of age) obese rats a proportionate increase in GAPDH activity and mRNA amounts was observed in adipose tissue, but not in liver. It is concluded that the obese genotype influences GAPDH gene expression at a pretranslational level and in a tissue-specific manner. This phenomenon could partly contribute to the hyperactive fat accretion in the obese rat, since glycolysis is the major metabolic pathway for lipogenic substrates in adipose tissue.

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