scholarly journals Altered Brain Cholinergic and Synaptic Markers in Obese Zucker Rats

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2528
Author(s):  
Ilenia Martinelli ◽  
Daniele Tomassoni ◽  
Proshanta Roy ◽  
Francesco Amenta ◽  
Seyed Khosrow Tayebati
Keyword(s):  
Frontal Cortex ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Body Weight Gain ◽  
Immunohistochemical Analysis ◽  
Zucker Rats ◽  
Lean Littermate ◽  
Synaptic Markers ◽  
Obese Zucker Rats

The association between obesity and loss of cognitive performance has been recognized. Although there are data regarding the metabolic alterations in obese conditions and the development of neuroinflammation, no clear evidence concerning obesity-related cholinergic and synaptic impairments in the frontal cortex and hippocampus has been reported yet. Here, we investigate different cholinergic and synaptic markers in 12-, 16-, and 20-week-old obese Zucker rats (OZRs) compared with lean littermate rats (LZRs), using immunochemical and immunohistochemical analysis. Consequently, OZRs showed body weight gain, hypertension, and dysmetabolism. In 20-week-old OZRs, the reduction of vesicular acetylcholine transporter (VAChT) and alpha7 nicotinic acetylcholine receptors (α7nAChR) occurred both in the frontal cortex and in the hippocampus, suggesting a cognitive dysfunction due to obesity and aging. Among the muscarinic receptors analyzed, the level of expression of type 1 (mAChR1) was lower in the hippocampus of the older OZRs. Finally, we showed synaptic dysfunctions in OZRs, with a reduction of synaptophysin (SYP) and synaptic vesicle glycoprotein 2B (SV2B) in 20-week-old OZRs, both in the frontal cortex and in the hippocampus. Taken together, our data suggest specific alterations of cholinergic and synaptic markers that can be targeted to prevent cognitive deficits related to obesity and aging.

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.

987 des-acyl Ghrelin Suppresses Food Intake and Body Weight Gain in Adult Obese Zucker Rats

2008 ◽  
Vol 134 (4) ◽  
pp. A-148 ◽  
Author(s):  
Andreas Stengel ◽  
Anna-Sophia Wisser ◽  
Peter Kobelt ◽  
Miriam Goebel ◽  
Bertram Wiedenmann ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Acyl Ghrelin

Sibutramine Decreases Body Weight Gain and Increases Energy Expenditure in Obese Zucker Rats without Changes in NPY and Orexins

2003 ◽  
Vol 6 (2) ◽  
pp. 103-111 ◽  
Author(s):  
A. Casado ◽  
V.M. Rodri´guez ◽  
M.P. Portillo ◽  
M.T. Macarulla ◽  
L.C. Abecia ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Body Weight Gain ◽  
Zucker Rats ◽  
Obese Zucker Rats

scholarly journals Reduction of renal dopamine receptor expression in obese Zucker rats: role of sex and angiotensin II

2010 ◽  
Vol 299 (5) ◽  
pp. F1164-F1170 ◽  
Author(s):  
Xiaoyan Wang ◽  
Fengmin Li ◽  
Pedro A. Jose ◽  
Carolyn M. Ecelbarger
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Expression ◽  
Female Rats ◽  
Male Rats ◽  
Zucker Rats ◽  
Protein Levels ◽  
Obese Rats ◽  
Obese Zucker Rats

Dopamine produced by renal proximal tubules increases sodium excretion via a decrease in renal sodium reabsorption. Dopamine natriuresis is impaired in obese Zucker rats; however, the mechanism is not fully understood. To test the hypothesis that renal expression of one or more of the subtypes are altered in these rats, we measured whole kidney protein levels by immunoblotting of D1-like (D1R and D5R) and D2-like (D2R, D3R, and D4R) dopamine receptors in both male and female obese and lean Zucker rats. In obese males on 1% NaCl diet, D1R, D2R, D4R, and D5R were decreased, while D3R was increased, relative to lean rats. Under a 4% NaCl diet, D2R and D3R levels in obese rats were restored to lean levels. 4% NaCl diet reduced D5R in both body types, relative to 1% NaCl diet. Female rats had higher expression of D1R and D3R than did male; however, the sex difference for D1R was markedly blunted in obese rats. In obese rats, dietary candesartan (angiotensin II type 1 receptor blocker) normalized downregulated D1R and D2R, but either decreased (D3R), did not affect (D4R), or further downregulated (D5R) the other subtypes. Candesartan also decreased D4R in lean rats. In summary, reduced renal protein levels of D1R, D2R, D4R, and D5R in obese Zucker rats could induce salt sensitivity and elevate blood pressure. Increased angiotensin II type 1 receptor activity may be mechanistically involved in the decreased expression of D1R and D2R in obese rats. Finally, reduced D1R and D3R in male rats may contribute to sex differences in blood pressure.

scholarly journals Dysregulation of glucocorticoid metabolism in murine obesity: comparable effects of leptin resistance and deficiency

2009 ◽  
Vol 201 (2) ◽  
pp. 211-218 ◽  
Author(s):  
Dawn E W Livingstone ◽  
Sarah L Grassick ◽  
Gillian L Currie ◽  
Brian R Walker ◽  
Ruth Andrew
Keyword(s):  
Reductase Activity ◽  
Leptin Resistance ◽  
Zucker Rats ◽  
Murine Models ◽  
Obese Zucker Rats ◽  
Visceral Adipose ◽  
Subcutaneous Adipose ◽  
Glucocorticoid Metabolism ◽  
Short Splice Variant

In obese humans, metabolism of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and A-ring reduction (by 5α- and 5β-reductases) is dysregulated in a tissue specific manner. These changes have been recapitulated in leptin resistant obese Zucker rats but were not observed in high-fat fed Wistar rats. Recent data from mouse models suggest that such discrepancies may reflect differences in leptin signalling. We therefore compared glucocorticoid metabolism in murine models of leptin deficiency and resistance. Male ob/ob and db/db mice and their respective littermate controls (n=10–12/group) were studied at the age of 12 weeks. Enzyme activities and mRNA expression were quantified in snap-frozen tissues. The patterns of altered pathways of steroid metabolism in obesity were similar in ob/ob and db/db mice. In liver, 5β-reductase activity and mRNA were increased and 11β-HSD1 decreased in obese mice, whereas 5α-reductase 1 (5αR1) mRNA was not altered. In visceral adipose depots, 5β-reductase was not expressed, 11β-HSD1 activity was increased and 5αR1 mRNA was not altered in obesity. By contrast, in subcutaneous adipose tissue 11β-HSD1 and 5αR1 mRNA were decreased. Systematic differences were not found between ob/ob and db/db murine models of obesity, suggesting that variations in leptin signalling through the short splice variant of the Ob receptor do not contribute to dysregulation of glucocorticoid metabolism.

scholarly journals Mechanisms of dysregulation of 11 beta-hydroxysteroid dehydrogenase type 1 in obese Zucker rats

2000 ◽  
Vol 167 (3) ◽  
pp. 533-539 ◽  
Author(s):  
DE Livingstone ◽  
CJ Kenyon ◽  
BR Walker
Keyword(s):  
Weight Gain ◽  
Hydroxysteroid Dehydrogenase ◽  
Zucker Rats ◽  
Tissue Specific ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
The Difference ◽  
Underlying Mechanisms ◽  
Omental Fat

Obesity has been associated with alterations in glucocorticoid metabolism in both man and rodents, but the underlying mechanisms remain undefined. We have previously reported tissue-specific alterations in 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) in obese Zucker rats predicting that reactivation of corticosterone is decreased in liver but increased in omental fat. The mechanisms of dysregulation of 11 beta-HSD1 in obesity are not known, and in this study we have investigated the potential role of glucocorticoids and insulin. In one experiment lean and obese Zucker rats were adrenalectomised, and in a second experiment they were sensitised to insulin by treatment with either metformin or rosiglitazone. Adrenalectomy (ADX) of obese animals attenuated weight gain, normalised hepatic 11 beta-HSD1 kinetics by an effect on V(max) (V(max)in sham-operated animals, 6.6+/-1.1 nmol/min per mg in lean vs 3.4+/-0.6 in obese, P<0.01; in ADX animals 5.9+/-1.1 in lean vs 6.9+/-1.8 in obese, NS), and reversed the difference in omental fat 11 beta-HSD1 activity (18.9+/-4.2% in lean ADX vs 8.2+/-2.3 in obese ADX, P=0.03). Both metformin and rosiglitazone improved insulin sensitivity in obese, but not lean animals, and had no effect on 11 beta-HSD1 activity in either liver or fat. However, both treatments normalised adrenal hypertrophy in obese animals (48+/-29 mg in obese vehicle vs 37+/-1.2 in metformin and 38+/-1.8 in rosiglitazone treated, both P<0.01), and rosiglitazone tended to attenuate hypercorticosteronaemia in obese rats. Neither treatment attenuated weight gain; in fact, weight gain was enhanced by rosiglitazone in obese rats. In summary, altered 11 beta-HSD1 activity in obese Zucker rats is reversible following adrenalectomy, but the mechanism is unclear since adrenalectomy also normalises many other metabolic abnormalities. The current study suggests that hyperinsulinaemia is not responsible for tissue-specific dysregulation of 11 beta-HSD1. However, insulin sensitisation did reverse adrenal hypertrophy, suggesting that hyperinsulinaemia may be a key factor contributing to activation of the hypothalamic- pituitary-adrenal (HPA) axis in obesity independently of tissue-specific changes in 11 beta-HSD1.

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