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.

scholarly journals Alterations in glomerular proteoglycan metabolism in experimental non-insulin dependent diabetes mellitus.

1993 ◽  
Vol 3 (10) ◽  
pp. 1694-1704
Author(s):  
P Fioretto ◽  
W F Keane ◽  
B L Kasiske ◽  
M P O'Donnell ◽  
D J Klein
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Zucker Rats ◽  
Dependent Diabetes Mellitus ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Insulin Dependent ◽  
Obese Zucker Rats

Glomerular proteoglycans (PG) are important in modulating extracellular matrix assembly and glomerular permselectivity. In the obese Zucker rat, an experimental model of non-insulin dependent diabetes mellitus, expansion of the mesangial matrix, and microalbuminuria occur before the development of overt renal disease. The in vivo incorporation of (35S)sulfate into glomerular PG in 12-wk-old obese Zucker rats at the onset of microalbuminuria was compared with that of 12-wk-old lean Zucker rats. Specific (35S)sulfate incorporation into glomerular PG over 8 h was increased by 57% in obese rats compared with lean rats, suggesting increased PG synthesis. However, at variance with the observation in experimental models of insulin-dependent diabetes mellitus, the proportion of total glomerular (35S)PG released by heparin treatment was unchanged. Heparan sulfate (HS)-PG constituted over 60% of radiolabeled de novo synthesized glomerular PG. Similar proportions of HS-PG were extracted from the glomeruli of obese and lean rats. Isolated glomeruli spontaneously released two HS-PG, which constituted approximately 30% of total glomerular (35S)PG. On the basis of their chromatographic and electrophoretic patterns, these PG were similar in obese and lean rats. Heparin treatment of isolated glomeruli released an additional HS-PG, which appeared to be derived primarily from the glomerular extracellular matrix compartment and not from the detergent soluble cell fraction. Heparin-releasable HS-PG from both the lean and obese Zucker rats eluted at a KAV of 0.31 from Sepharose CL-6B chromatographic columns, indicating a hydrodynamic size similar to that reported for glomerular basement membrane HS-PG. However, gel electrophoresis demonstrated faster migration of the HS-PG released by heparin from the glomeruli of obese Zucker rats, suggesting increased electronegativity. Thus, early in the course of nephropathy in the obese Zucker rat, there is increased glomerular PG synthesis with no change in the proportions of the constitutively releasable and heparin-releasable HS-PG. Whether electrophoretic abnormalities of the heparin-releasable HS-PG observed in the obese rats contribute to the development of albuminuria and/or mesangial matrix expansion remains to be established.

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.

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.

scholarly journals 2060 Exploring gene expression signature shared between obese Zucker rat and human cardiac hypertrophy

2018 ◽  
Vol 2 (S1) ◽  
pp. 11-11
Author(s):  
Mackenzie Newman ◽  
Janelle Stricker ◽  
Han-Gang Yu
Keyword(s):  
Cardiac Hypertrophy ◽  
Drug Target ◽  
Model Organism ◽  
Gene Expression Signature ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Future Directions ◽  
Obese Zucker Rat ◽  
Study Population ◽  
Obese Zucker Rats

OBJECTIVES/SPECIFIC AIMS: Objectives: To determine genes that are shared between human and obese Zucker rat hypertrophic hearts, in order to identify potential early biomarkers and drug target for heart failure. METHODS/STUDY POPULATION: Four age-paired lean and obese Zucker rats were used. The human data are derived from doi:10.1152/physiolgenomics.00122.2016. RESULTS/ANTICIPATED RESULTS: We expect to find genes that are upregulated and downregulated in Zucker rats and humans that present cardiac hypertrophy. DISCUSSION/SIGNIFICANCE OF IMPACT: The genes and proteins determined from this study will provide future directions in order to determine whether obese Zucker rats are a valid model organism for the development of cardiac hypertrophy.

scholarly journals Changes in content and secretion of pancreatic enzymes in the obese Zucker rat

1984 ◽  
Vol 219 (1) ◽  
pp. 333-336 ◽  
Author(s):  
R Bruzzone ◽  
E R Trimble ◽  
A Gjinovci ◽  
A E Renold
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Digestive Enzymes ◽  
Enzyme Secretion ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Old Rats ◽  
Obese Zucker Rats

The contents of three major digestive enzymes (amylase, lipase and chymotrypsinogen) were measured in the obese Zucker rat. Only minimal changes were found in 7-week-old rats, but in adult obese rats (14-16 weeks) the amylase content was decreased by 50%, whereas the lipase and chymotrypsinogen contents were increased by 45% and 20%, respectively, compared with lean controls. Abnormalities of enzyme secretion were also found. Since the changes observed in enzyme proportions in adult obese Zucker rats are qualitatively similar to those observed in insulinopenic diabetes and other states associated with decreased glucose metabolism, it is speculated that the abnormalities found in the obese Zucker rat may be due to decreased glucose metabolism in the exocrine tissue consequent to insulin resistance.

Skeletal muscle contraction stimulates capillary recruitment and glucose uptake in insulin-resistant obese Zucker rats

2004 ◽  
Vol 287 (4) ◽  
pp. E804-E809 ◽  
Author(s):  
Catherine M. Wheatley ◽  
Stephen Rattigan ◽  
Stephen M. Richards ◽  
Eugene J. Barrett ◽  
Michael G. Clark
Keyword(s):  
Muscle Contraction ◽  
Glucose Uptake ◽  
Lower Leg ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Capillary Recruitment ◽  
Obese Zucker Rat ◽  
Impaired Insulin ◽  
Obese Zucker Rats

Exercise and insulin increase muscle glucose uptake by different mechanisms and also increase capillary recruitment, which is proposed to facilitate access for hormones and nutrients. The genetically obese Zucker rat shows impaired insulin- but not contraction-mediated glucose uptake in muscle. Recently, we have shown the genetically obese Zucker rats to have impaired insulin-mediated capillary recruitment and proposed that this contributes to the insulin resistance of muscle in vivo. Because this might imply a general loss of recruitable capillaries, we now assess responses to contraction in muscles of 18 ± 3-wk-old lean and obese Zucker rats in vivo. Field stimulation (2 Hz, 0.1 ms) was conducted for 1 h on one leg of anesthetized instrumented rats, and measurements were made of femoral blood flow (FBF), heart rate (HR), blood pressure (BP), hindleg metabolism of 1-methylxanthine (a measure of capillary recruitment), hindleg glucose uptake (HGU), and lower leg muscle glucose uptake by 2-deoxyglucose (R′g). Lean animals (311 ± 9 g) developed tension at 219 ± 27 g/g muscle with no change in BP but with significant increases in HR, FBF, HGU, 1-MX metabolism, and R′g ( P < 0.05), compared with nonstimulated control leans. Obese animals (469 ± 7 g) developed tension at 265 ± 31 g/g muscle with no change in HR or BP but with significant increases in FBF, HGU, 1-MX metabolism, and R′g ( P < 0.05) compared with nonstimulated control obese rats. Muscle contraction of lean animals led to a greater increase in lower leg R′g, similar responses in HGU and 1-MX, and a smaller increase in FBF than in obese animals. A tight correlation between FBF and capillary recruitment was noted for all data ( P < 0.001). It is concluded that contraction-mediated muscle capillary recruitment and glucose uptake are essentially normal in the obese Zucker rat and that control of FBF and capillary recruitment in exercise is closely linked.

Exercise, unlike insulin, promotes glucose transporter translocation in obese Zucker rat muscle

1993 ◽  
Vol 265 (2) ◽  
pp. R447-R452 ◽  
Author(s):  
P. A. King ◽  
J. J. Betts ◽  
E. D. Horton ◽  
E. S. Horton
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Plasma Membranes ◽  
Acute Exercise ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Rat Muscle ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
Muscle Glucose Transport

Insulin or exercise stimulates skeletal muscle glucose transport, most likely by increasing both the number and activity of glucose transporters in the plasma membrane. Skeletal muscle glucose transport of genetically obese Zucker rats (fa/fa) displays a severe insulin resistance that results, at least in part, from a failure of net transporter translocation to the cell membrane (King, P., E. D. Horton, M. Hirshman, and E. S. Horton. J. Clin, Invest. 90: 1568-1575, 1992). The purpose of the present study was to determine if the obese rat muscle was also resistant to the action of acute exercise to increase glucose transport and, if so, to determine if the defect involved transporter translocation as seen in the resistance to insulin. The muscle glucose transport system was investigated in plasma membranes isolated from postprandial, sedentary or acutely exercised, lean and obese Zucker rats. Measurements of D- and L-glucose uptake by membrane vesicles under equilibrium exchange conditions indicated that an acute bout of exercise resulted in a threefold increase in the maximum velocity (Vmax) for lean animals (5.7 vs. 17.6 nmol.mg protein-1.min-1) and a 4.5-fold increase in the Vmax for obese rats (4.1 vs. 18.6 nmol.mg protein-1.min-1). For both lean and obese animals, this increase in transport was associated with an increase in transporter number measured by cytochalasin B binding (1.6- and 2.2-fold, respectively) and with an increase in the average carrier turnover number (1.9- and 2.0-fold, respectively). The results indicate that, unlike a maximal insulin stimulus, acute exercise of the obese Zucker rat promotes both transporter translocation and transporter activation in skeletal muscle.

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.

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