scholarly journals Metabolic Status of Lean and Obese Zucker Rats Based on Untargeted and Targeted Metabolomics Analysis of Serum

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 153
Author(s):  
Stepan Melnyk ◽  
Reza Hakkak
Keyword(s):  
Animal Models ◽  
Kynurenic Acid ◽  
Peak Height ◽  
Zucker Rats ◽  
Targeted Metabolomics ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
Treatment Of Obesity ◽  
The Individual ◽  
Metabolomics Analysis

Obesity is growing worldwide epidemic. Animal models can provide some clues about the etiology, development, prevention, and treatment of obesity. We examined and compared serum metabolites between seven lean (L) and seven obese (O) female Zucker rats to investigate the individual serum metabolic profile. A combination of HPLC-UV, HPLC-ECD, and LC-MS revealed more than 400 peaks. The 50 highest quality peaks were selected as the focus of our study. Untargeted metabolomics analysis showed significantly higher mean peak heights for 20 peaks in L rats, generally distributed randomly, except for a cluster (peaks 44–50) where L showed stable dominancy over O. Only eight peaks were significantly higher in O rats. Peak height ratios between pairs of L and O rats were significantly higher at 199 positions in L rats and at 123 positions in O rats. Targeted metabolomics analysis showed significantly higher levels of methionine, cysteine, tryptophan, kynurenic acid, and cysteine/cystine ratio in L rats and significantly higher levels of cystine and tyrosine in O rats. These results contribute to a better understanding of systemic metabolic perturbations in the obese Zucker rat model, emphasizing the value of both whole metabolome and individual metabolic profiles in the design and interpretation of studies using animal models.

scholarly journals The age-related increase in renal clusterin mRNA is accelerated in obese Zucker rats.

1998 ◽  
Vol 9 (1) ◽  
pp. 38-45 ◽  
Author(s):  
N J Laping ◽  
B A Olson ◽  
J R Day ◽  
B M Brickson ◽  
L C Contino ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tissue Injury ◽  
Rat Kidney ◽  
Zucker Rats ◽  
Mrna Levels ◽  
Zucker Rat ◽  
Age Related ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
F344 Rats

Clusterin is a multifunctional glycoprotein associated with development and tissue injury. Because renal function decreases with advancing age in the obese Zucker rat, clusterin mRNA expression was examined in the kidney of young adult Zucker rats and compared with age-related changes in renal clusterin mRNA expression in Fischer 344 (F344) rats. Renal clusterin mRNA levels in the obese Zucker rat were 2.5-fold higher by 3 mo of age and fourfold higher at 5 mo of age compared with the lean strain. In comparison, renal clusterin mRNA in 12-mo-old F344 rats was twofold higher than in 3-mo-old animals and was tenfold higher at 24 mo of age. Clusterin mRNA was positively correlated with urinary protein excretion and negatively correlated with creatinine clearance in Zucker rats. Clusterin was increased in select nephrons of the obese Zucker rat kidney and in 24-mo-old F344 rat kidney as assessed by in situ hybridization. Increased expression of clusterin mRNA occurred mostly in the tubular epithelium of dilated, convoluted proximal tubules. These data indicate that renal clusterin mRNA levels increase as a function of age and that age-related increases in renal clusterin and the associated tubular abnormalities are accelerated in obese Zucker rats.

scholarly journals Mechanism controlling sleep organization of the obese Zucker rats

1998 ◽  
Vol 84 (1) ◽  
pp. 253-256 ◽  
Author(s):  
David Megirian ◽  
Jacek Dmochowski ◽  
Gaspar A. Farkas
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Zucker Rats ◽  
Rapid Eye Movement ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
The Mean

Megirian, David, Jacek Dmochowski, and Gaspar A. Farkas. Mechanism controlling sleep organization of the obese Zucker rat. J. Appl. Physiol. 84(1): 253–256, 1998.—We tested the hypothesis that the obese ( fa/fa) Zucker rat has a sleep organization that differs from that of lean Zucker rats. We used the polygraphic technique to identify and to quantify the distribution of the three main states of the rat: wakefulness (W), non-rapid-eye-movement (NREM), and rapid-eye-movement (REM) sleep states. Assessment of states was made with light present (1000–1600), at the rats thermoneutral temperature of 29°C. Obese rats, compared with lean ones, did not show significant differences in the total time spent in the three main states. Whereas the mean durations of W and REM states did not differ statistically, that of NREM did ( P = 0.046). However, in the obese rats, the frequencies of switching from NREM sleep to W, which increased, and from NREM to REM sleep, which decreased, were statistically significantly different ( P = 0.019). Frequency of switching from either REM or W state was not significantly different. We conclude that sleep organization differs between lean and obese Zucker rats and that it is due to a disparity in switching from NREM sleep to either W or REM sleep and the mean duration of NREM sleep.

Decreased epoxygenase and increased epoxide hydrolase expression in the mesenteric artery of obese Zucker rats

2005 ◽  
Vol 288 (1) ◽  
pp. R188-R196 ◽  
Author(s):  
Xueying Zhao ◽  
Aparajita Dey ◽  
Olga P. Romanko ◽  
David W. Stepp ◽  
Mong-Heng Wang ◽  
...  
Keyword(s):  
Mesenteric Artery ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Mesenteric Arteries ◽  
Zucker Rats ◽  
Epoxyeicosatrienoic Acids ◽  
Obese Zucker Rat ◽  
Protein Expressions ◽  
Obese Zucker Rats ◽  
Cytochrome P 450

Previous studies suggest that epoxyeicosatrienoic acids (EETs) are vasodilators of the mesenteric artery; however, the production and regulation of EETs in the mesenteric artery remain unclear. The present study was designed 1) to determine which epoxygenase isoform may contribute to formation of EETs in mesenteric arteries and 2) to determine the regulation of mesenteric artery cytochrome P-450 (CYP) enzymes in obese Zucker rats. Microvessels were incubated with arachidonic acid, and CYP enzyme activity was determined. Mesenteric arteries demonstrate detectable epoxygenase and hydroxylase activities. Next, protein and mRNA expressions were determined in microvessels. Although renal microvessels express CYP2C23 mRNA and protein, mesenteric arteries lacked CYP2C23 expression. CYP2C11 and CYP2J mRNA and protein were expressed in mesenteric arteries and renal microvessels. In addition, mesenteric artery protein expression was evaluated in lean and obese Zucker rats. Compared with lean Zucker rats, mesenteric arterial CYP2C11 and CYP2J proteins were decreased by 38 and 43%, respectively, in obese Zucker rats. In contrast, soluble epoxide hydrolase mRNA and protein expressions were significantly increased in obese Zucker rat mesenteric arteries. In addition, nitric oxide-independent dilation evoked by acetylcholine was significantly attenuated in mesenteric arteries of obese Zucker rats. These data suggest that the main epoxygenase isoforms expressed in mesenteric arteries are different from those expressed in renal microvessels and that decreased epoxygenases and increased soluble epoxide hydrolase are associated with impaired mesenteric artery dilator function in obese Zucker rats.

Adenohypophyseal response to hypophysiotropic hormones in male obese Zucker rats

1985 ◽  
Vol 249 (4) ◽  
pp. E380-E384
Author(s):  
M. L. Heiman ◽  
J. R. Porter ◽  
M. V. Nekola ◽  
W. A. Murphy ◽  
A. D. Hartman ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Amino Acid ◽  
Luteinizing Hormone ◽  
Zucker Rats ◽  
Pituitary Cells ◽  
Response Curves ◽  
Amino Acid Molecule ◽  
Obese Zucker Rat ◽  
Recessive Homozygote ◽  
Obese Zucker Rats

Description of the recessive, homozygote obese Zucker rat (fafa) includes disorders of growth and reproduction. The aim of this study was to compare responsiveness of adenohypophyseal cells, obtained from male fafa rats and from their lean siblings, to growth hormone-releasing factor (GRF) and to luteinizing hormone-releasing hormone (LHRH). Pituitary cells were cultured for 4 days and were then challenged with either GRF-29 (the NH2-terminal 29 amino acid GRF peptide that expresses full biological activity of its parent 44 amino acid molecule) or [D-Trp6]LHRH (LHRH-A, an LHRH agonist). Medium was assayed for growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by radioimmunoassay. Dose-response curves were compared using the computer program ALLFIT. The median effective GRF-29 concentration (EC50) computed for hypophyseal cells cultured from lean animals (0.30 +/- 0.01 fM; means +/- SE of 4 experiments) was less (P less than 0.01) than that calculated for cells obtained from fafa rats (15.8 +/- 6.7 fM). In contrast, cells derived from lean littermates required a larger (EC50) concentration of LHRH-A than did gonadotrophs cultured from obese rats [58.2 +/- 1.2 vs. 10.7 +/- 1.2 pM (P less than 0.01) and 59.4 +/- 10.4 vs. 15.7 +/- 7.6 pM (P less than 0.05)] to secrete LH and FSH, respectively. Our data describe an attenuated pituitary response to GRF-29 and an enhanced response to LHRH-A in the fafa.

scholarly journals Dietary modulation of ghrelin and leptin and gorging behavior after weight loss in the obese Zucker rat

2009 ◽  
Vol 202 (1) ◽  
pp. 29-34 ◽  
Author(s):  
B Beck ◽  
S Richy
Keyword(s):  
Weight Loss ◽  
Calorie Restriction ◽  
High Energy ◽  
Zucker Rats ◽  
Constant Intensity ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
Palatable Diet ◽  
Plasma Leptin ◽  
Very High

In this study, we measured ghrelin and leptin in obese Zucker rats after weight loss induced by calorie restriction using either a low-fat (LF) or high-energy palatable (HEPa) diet. After weight loss, the animals were refed lab chow and offered one hour-palatable test meals on the second and fifteenth days of refeeding. Both LF and HEPa rats lost 10% of their initial body weight (P<0.0001). Plasma ghrelin increased with calorie restriction in both groups (P<0.002) with a tendency to a higher increase in the HEPa group while plasma leptin decreased only in the LF group (P<0.01). Both groups ate the same quantity of chow during refeeding and both groups gorged on palatable diet during test meals at a very high constant intensity in HEPa rats. After one week of refeeding, ghrelin levels remained elevated in HEPa rats (+33.2%; P<0.001) while returning to baseline in LF rats. Plasma leptin remained low in LF rats. We conclude that weight loss on a palatable diet is possible if total energy intake is controlled. After stopping restriction, when a palatable diet is available, observed gorging might be dependent on specific ghrelin and leptin changes.

Impaired Insulin-Induced Attenuation of Noradrenaline-Mediated Vasoconstriction in Insulin-Resistant Obese Zucker Rats

1997 ◽  
Vol 93 (3) ◽  
pp. 235-241 ◽  
Author(s):  
A. B. Walker ◽  
J. Dores ◽  
R. E. Buckingham ◽  
M. W. Savage ◽  
G. Williams
Keyword(s):  
Underlying Mechanism ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Obese Zucker Rat ◽  
Maximal Tension ◽  
Impaired Insulin ◽  
Obese Rats ◽  
Significant Impairment ◽  
Obese Zucker Rats ◽  
L 13

1. Insulin resistance is associated with hypertension but the underlying mechanism is unclear. We tested the hypothesis that insulin-induced vasodilatation is impaired in insulin-resistant obese Zucker rats. We studied mesenteric artery (≈ 220 μm diameter) function before the development of hypertension in 3-month old obese Zucker rats and age-matched lean rats. 2. In vessels from lean rats, insulin at concentrations of 50, 500 and 5000 m-units/l attenuated the constriction in response to noradrenaline (50 m-units/l: 8 ± 3%, P < 0.05; 500 m-units/l: 13 ± 3%, P < 0.02; 5000 m-units/l: 13 ± 2%, P < 0.02). 3. Vessels from obese rats failed to show any such response to insulin (2 ± 6% increase in maximal tension with 5000 m-units/l; not significant), both in the presence and absence of l-arginine (3 mmol/l). 4. Vessels from obese rats showed slight but significant impairment in the vasodilator response to acetylcholine (5 × 10−8−10−4 mol/l) (obese: 64.1 ± 3.7% relaxation; lean: 77.3 ± 3.7% relaxation; P < 0.05); however, relaxation in response to A23187 was not significantly different between the phenotypes (obese: 81.3 ± 10.6% relaxation; lean: 79.1 ± 9.7% relaxation; not significant). 5. Systolic blood pressure was not significantly different in lean (126 ± 8 mmHg) and obese (127 ± 7 mmHg) rats at the time of study (not significant). 6. We conclude that insulin-induced attenuation of noradrenaline-mediated vasoconstriction is impaired in the obese Zucker rat and that this defect precedes and therefore could contribute to the development of hypertension in this insulin-resistant model. The defect in insulin action could reside in the endothelial generation of nitric oxide, as endothelial function is also abnormal.

scholarly journals Adipsin mRNA amounts are not decreased in the genetically obese Zucker rat

1989 ◽  
Vol 257 (3) ◽  
pp. 917-919 ◽  
Author(s):  
I Dugail ◽  
X Le Liepvre ◽  
A Quignard-Boulangé ◽  
J Pairault ◽  
M Lavau
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Obese Mice ◽  
High Fat ◽  
Adult Rats ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Obese Zucker Rats

Adipsin gene expression as assessed by mRNA amounts was examined in adipose tissue of genetically obese rats at the onset (16 days of age) or at later stages (30 and 60 days of age) of obesity. Amounts of mRNA were equivalent in obese and lean rats at 16 days of age. In adult rats, we observed a 2-fold decrease in adipsin mRNA in the obese rats compared with control lean rats, which was abolished by weaning the animals on a high-fat diet. Our data show that, in sharp contrast with genetically obese mice, adipsin mRNA is not suppressed in genetically obese Zucker rats.

Reduced renal responses to an acute saline load in obese Zucker rats

1991 ◽  
Vol 261 (3) ◽  
pp. R712-R718 ◽  
Author(s):  
D. W. Zeigler ◽  
K. P. Patel
Keyword(s):  
Blood Pressure ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Urine Flow ◽  
Reflex Response ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
Renal Responses

The purpose of this study was to determine if the reflex response to a saline load is altered in the obese Zucker rat. The obese Zucker rat is a genetic model of obesity and insulin-resistant diabetes that has been reported to have high blood pressure. We examined the reflux renal responses to volume expansion in both anesthetized obese and lean Zucker rats. Initial blood pressure was significantly elevated in the obese Zucker rats compared with the lean controls. Urine flow and sodium excretion from innervated and denervated kidneys were measured before and after volume expansion with normal saline. Volume expansion resulted in significantly less urine flow and sodium excretion in the obese than the lean Zucker rats. This response was evident in both the intact and denervated kidneys. Rats were then infused with atrial natriuretic peptide (ANP) to determine if natriuretic and diuretic responses were altered in these rats. The diuretic action of ANP was not significantly reduced in the obese Zucker rat. However, the natriuretic action of ANP was significantly attenuated in the obese rats. These results indicate that the reflux response to an acute saline load is attenuated in the obese Zucker rat and that this decreased response may be due to a reduction in the direct action of ANP on the kidney.

Increased SMC proliferation after endothelial injury in hyperinsulinemic obese Zucker rats

1994 ◽  
Vol 267 (5) ◽  
pp. H1976-H1983 ◽  
Author(s):  
S. Ridray ◽  
D. Heudes ◽  
O. Michel ◽  
L. Penicaud ◽  
A. Ktorza
Keyword(s):  
Dna Synthesis ◽  
Endothelial Injury ◽  
Zucker Rats ◽  
Inflated Balloon ◽  
Endothelial Denudation ◽  
Long Term Effect ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Nuclear Number

The long-term effect of long-lasting hyperinsulinemia on aortic smooth muscle cell (SMC) proliferation after endothelial injury was investigated using the obese Zucker rat model, which is characterized especially by early spontaneous development of hyperinsulinemia and insulin resistance. SMC proliferation was provoked by the passage of an embolectomy catheter with a tightly inflated balloon and was assessed by measuring the incorporation of [3H]thymidine in the DNA of intima-media layers. Compared with controls, the SMC mitotic activity was not significantly increased from day 2 to day 7 after injury, but from day 14 to day 30 after endothelial denudation, SMC proliferation was significantly less decreased in obese than in lean rats [on day 14, DNA synthesis = 107 +/- 18 counts.min-1.micrograms DNA-1 in lean and 345 +/- 44 counts.min-1.micrograms DNA-1 in obese rats (P = 0.003); and on day 30, DNA synthesis = 74 +/- 18 counts.min-1.micrograms DNA-1 in lean and 133 +/- 19 counts.min-1.micrograms DNA-1 in obese rats (P = 0.0055)]. As a result, the intima-media DNA content was higher in obese than in lean rats on day 14 and even more so on day 30, suggesting a higher amount of SMCs in the intima-media. Moreover, on day 30, the aortic thickening, as measured by a histomorphometric technique, was much higher in obese than in lean rats. This difference was entirely due to an increase in SMC content of the intima, mainly resulting from a dramatic increment in the number of nuclei and nuclear number density.(ABSTRACT TRUNCATED AT 250 WORDS)

Pyruvate carboxylase in genetic obesity

1992 ◽  
Vol 262 (5) ◽  
pp. E608-E618 ◽  
Author(s):  
C. J. Lynch ◽  
K. M. McCall ◽  
M. L. Billingsley ◽  
L. M. Bohlen ◽  
S. P. Hreniuk ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pyruvate Carboxylase ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Rat Adipocytes ◽  
Obese Zucker Rat ◽  
Streptozotocin Induced Diabetes ◽  
Obese Zucker Rats ◽  
Relative Molecular Weight ◽  
Polyclonal Antisera

Immunoblotting and protein microsequencing were used to identify several adipocyte proteins expressed in an obesity-related fashion in the Zucker rat. One of these was a 116-kDa particulate protein (p116). The p116 levels in adipocytes from 5- to 7-wk-old obese Zucker rats were two- to fivefold higher on a per milligram of protein basis than levels in lean animals and decreased after the induction of streptozotocin-induced diabetes mellitus. This suggests the change may be related to the actions of insulin. Hepatic levels of p116 did not change. The p116 was purified to homogeneity from obese Zucker rat adipocytes, and polyclonal antisera were prepared against the purified protein in rabbits. Microanalysis of electroblotted p116 proteolytic fragments suggested that p116 was pyruvate carboxylase (PC). Other evidence that p116 was PC included the following: 1) p116 contained biotin, 2) p116 in particulate subcellular fractions was soluble after freeze-lysis, 3) antibodies to p116 reacted with purified hepatic PC, 4) p116 and purified hepatic PC had identical pI and relative molecular weight values, and 5) similar changes were detected in adipocyte p116 and PC enzyme activity during obesity and after the induction of streptozotocin-induced diabetes mellitus. Increased adipose tissue PC probably contributes to the increased lipogenic capacity of young obese Zucker rat adipocytes.

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