Muscle bioenergetics in obese Zucker rats

1994 ◽  
Vol 266 (3) ◽  
pp. E410-E417 ◽  
Author(s):  
M. Klein ◽  
P. Kaminsky ◽  
P. M. Walker ◽  
J. Straczek ◽  
F. Barbe ◽  
...  
Keyword(s):  
Inorganic Phosphate ◽  
Zucker Rats ◽  
Resonance Spectroscopy ◽  
Muscle Stimulation ◽  
Energetic Metabolism ◽  
Subsequent Recovery ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Total Creatine

The purpose of this study was to investigate the energetic metabolism in obese Zucker rats, using phosphorus nuclear magnetic resonance spectroscopy at rest and during a 2-Hz muscle stimulation and subsequent recovery. Animals were anesthetized with ketamine (150 mg/kg ip). Fed obese rats and 2-day-fasted obese rats were compared with their normally fed and 2-day-fasted lean litter mates. No differences were found between the two groups for ATP, total creatine, phosphocreatine (PCr), and intracellular pH. Starvation in lean rats resulted in a significant fall in inorganic phosphate (Pi), increased resting ADP level, and decreased PCr and ADP recovery after stimulation. The obese rats exhibited a decreased PCr/Pi and increased ADP at rest and a decreased PCr resynthesis and ADP metabolization rate after stimulation. Muscle stimulation in fasted obese rats induced higher PCr depletion and more pronounced acidosis. These results suggest an in vivo mitochondrial metabolism dysfunction in fasted lean as well as in fed and fasted obese rats.

Obesity lowers hyperglycemic threshold for impaired in vivo endothelial nitric oxide function

2002 ◽  
Vol 283 (1) ◽  
pp. H391-H397 ◽  
Author(s):  
H. G. Bohlen ◽  
Geoffrey P. Nase
Keyword(s):  
Nitric Oxide ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Zucker Rats ◽  
Kinase C ◽  
Lower Glucose ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Endothelial Nitric Oxide

Obesity is a risk for type II diabetes mellitus and increased vascular resistance. Disturbances of nitric oxide (NO) physiology occur in both obese animals and humans. In obese Zucker rats, we determined whether a protein kinase C-βII (PKC-βII) mechanism may lower the resting NO concentration ([NO]) and predispose endothelial NO abnormalities at lower glucose concentrations than occur in lean rats. NO was measured with microelectrodes touching in vivo intestinal arterioles. At rest, the [NO] in obese Zucker rats was 60 nm less than normal or about a 15% decline. After local blockade of PKC-βII with LY-333531, the [NO] increased ∼90 nm in obese rats but did not change in lean rats. In lean rats, administration of 300 mg/dl d-glucose for 45 min depressed endothelium-dependent dilation; only 200 mg/dl was required in obese animals. These various observations indicate that resting [NO] is depressed in obese rats by a PKC-βII mechanism and the hyperglycemic threshold for endothelial NO suppression is reduced to 200 mg/dl d-glucose.

scholarly journals Regulation of the renal thiazide-sensitive Na-Cl cotransporter, blood pressure, and natriuresis in obese Zucker rats treated with rosiglitazone

2005 ◽  
Vol 289 (2) ◽  
pp. F442-F450 ◽  
Author(s):  
Osman Khan ◽  
Shahla Riazi ◽  
Xinqun Hu ◽  
Jian Song ◽  
James B. Wade ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Control Diet ◽  
Zucker Rats ◽  
Receptor Subtype ◽  
Protein Abundance ◽  
Lean Control ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Nacl Load

Previously, we showed an increase in protein abundance of the renal thiazide-sensitive Na-Cl cotransporter (NCC) in young, prediabetic, obese Zucker rats relative to lean age mates (Bickel CA, Verbalis JF, Knepper MA, and Ecelbarger CA. Am J Physiol Renal Physiol 281: F639–F648, 2001). To test whether this increase correlated with increased thiazide sensitivity (NCC activity) and blood pressure, and could be modified by insulin-sensitizing agents, we treated lean and obese Zucker rats (9 wk old) with either a control diet or this diet supplemented with 3 mg/kg body wt rosiglitazone (RGZ), a peroxisomal proliferator-activated receptor subtype γ agonist and potent insulin-sensitizing agent, for 12 wk ( n = 9/group). The rise in blood pressure, measured continuously by radiotelemetry, was significantly blunted in the RGZ-treated obese rats. Similarly, blood glucose and urinary albumin were markedly decreased in these rats. RGZ-treated rats whether lean or obese excreted a NaCl load faster but excreted less sodium in response to hydrochlorothiazide, applied as a novel in vivo measure of NCC activity. Obese rats had increased renal protein abundance and urinary excretion of NCC; however, this was not significantly reduced by RGZ (densitometry in cortex homogenate − %lean control): 100 ± 9, 93 ± 4, 124 ± 9, and 141 ± 14 for lean control, lean RGZ, obese control, and obese RGZ, respectively. Subcellular localization, as evaluated by confocal microscopy and immunoblotting following differential centrifugation, of NCC was not different between rat groups. Overall, RGZ reduced blood pressure and thiazide sensitivity; however, the mechanism(s) did not seem to involve a decrease in NCC protein abundance or cellular location. Decreased NCC activity may have contributed to the maintenance of normotension in RGZ-treated obese rats.

scholarly journals Roles of Fatty Acid Oversupply and Impaired Oxidation in Lipid Accumulation in Tissues of Obese Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Nicholas D. Oakes ◽  
Ann Kjellstedt ◽  
Pia Thalén ◽  
Bengt Ljung ◽  
Nigel Turner
Keyword(s):  
Fatty Acid ◽  
Lipid Accumulation ◽  
Ex Vivo ◽  
Oxidative Capacity ◽  
Whole Body ◽  
Zucker Rats ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
And Storage

To test the roles of lipid oversupply versus oxidation in causing tissue lipid accumulation associated with insulin resistance/obesity, we studiedin vivofatty acid (FA) metabolism in obese (Obese) and lean (Lean) Zucker rats. Indices of local FA utilization and storage were calculated using the partially metabolizable [9,10-3H]-(R)-2-bromopalmitate (3H-R-BrP) and [U-14C]-palmitate (14C-P) FA tracers, respectively. Whole-body FA appearance (Ra) was estimated from plasma14C-P kinetics. Whole-body FA oxidation rate (Rox) was assessed using3H2O production from3H-palmitate infusion, and tissue FA oxidative capacity was evaluatedex vivo. In the basal fasting state Obese had markedly elevated FA levels andRa, associated with elevated FA utilization and storage in most tissues. Estimated rates of muscle FA oxidation were not lower in obese rats and were similarly enhanced by contraction in both lean and obese groups. At comparable levels of FA availability, achieved by nicotinic acid,Roxwas lower in Obese than Lean. In Obese rats, FA oxidative capacity was 35% higher than that in Lean in skeletal muscle, 67% lower in brown fat and comparable in other organs. In conclusion, lipid accumulation in non-adipose tissues of obese Zucker rats appears to result largely from systemic FA oversupply.

scholarly journals In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Do-Wan Lee ◽  
Jae-Im Kwon ◽  
Chul-Woong Woo ◽  
Hwon Heo ◽  
Kyung Won Kim ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Rat Model ◽  
Resonance Spectroscopy ◽  
Chow Diet ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
In Vivo Measurement ◽  
Hippocampal Lesions ◽  
Total Creatine

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

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.

Blood flow to brown fat in lean and obese adrenalectomized Zucker rats

1986 ◽  
Vol 251 (5) ◽  
pp. R851-R858
Author(s):  
S. J. Wickler ◽  
B. A. Horwitz ◽  
J. S. Stern
Keyword(s):  
Blood Flow ◽  
Weight Gain ◽  
Brown Fat ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Nonshivering Thermogenesis ◽  
Brown Adipose ◽  
Obese Rats

The Zucker obese rat is characterized by decreased capacity for diet-induced and for nonshivering thermogenesis. This decrease is due, in large part, to reduced thermogenesis in depots of brown adipose tissue, a major source of heat production in rats. Adrenalectomy retards the weight gain observed in the obese rats and also normalizes brown fat guanosine 5'-diphosphate (GDP) binding, an in vitro measure of brown fat thermogenic capacity. This study examined the effect of adrenalectomy on brown fat blood flow, an in vivo measure of the tissue's function, and on norepinephrine-induced O2 consumption (NST) of 11-wk-old obese (fa/fa) and lean (Fa/?) rats. Adrenalectomy had little effect on weight gain, NST, or norepinephrine-stimulated blood flow to brown fat in lean rats. However, adrenalectomy produced profound changes in the obese animals, preventing the weight gain normally occurring in the obese rats and normalizing both NST capacity and norepinephrine-stimulated blood flow to brown fat. These findings provide further support for the importance of brown fat thermogenesis and glucocorticoids in modulating the obesity of the Zucker rat.

Abstract P184: Co-localization and Natriuretic Interdependence of Angiotensin AT2R and MasR in Obese Rat Kidney

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sanket N Patel ◽  
Quaisar Ali ◽  
Ulrike Muscha Steckelings ◽  
Tahir Hussain
Keyword(s):  
Rat Kidney ◽  
Sulfhydryl Groups ◽  
Zucker Rats ◽  
Diabetic Rat ◽  
Physical Interaction ◽  
Potential Mechanism ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Made In

The actions of angiotensin II type 2 receptor (AT 2 R) and receptor mas (MasR) are complex but show similar pro-natriuretic function; particularly AT 2 R expression and natriuretic function are enhanced in obese/diabetic rat kidney. In light of previous reports, we tested hypothesis that AT 2 R and MasR are interdependent to produce natriuresis in obese rats due to potential physical interaction. Infusion of AT 2 R agonist C21 (5 μg/kg/min) in obese Zucker rats (OZR) caused diuresis/natriuresis which were attenuated by simultaneous infusion of the AT 2 R antagonist PD123319 (50 μg/kg/min) or the MasR antagonist A-779 (50 μg/kg/min). Similarly, infusion of MasR agonist Ang-(1-7) (110 fmol/kg/min) in OZR caused diuresis/netriuresis, which were attenuated by simultaneous infusion of A-779 or PD123319. Dual labeling of AT 2 R and MasR in OZR kidney slices revealed four-fold co-localization of AT 2 R and MasR (9.83 vs. 2.50 dual labeled cells/1600 μm 2 ) compared with lean rats in which AT 2 R is not natriuretic. Moreover, the AT 2 R co-immunoprecipitates with MasR in cortical homogenate of OZR. Immunoblotting of AT 2 R and MasR with zero length oxidative (sulfhydryl groups) cross-linker cupric-phenanthroline in OZR cortical homogenate revealed a shift of AT 2 R (~62 kDa) and MasR (~54 kDa) bands upward with overlapping migration for their complexes (~160 kDa and 245 kDa) which were sensitive to the reducing β-mercaptoethanol. Similar observations were made in HK-2 cells, where glucose (25 mM) treatment enhanced the crosslinking. Collectively, the study reveals AT2R and MasR are co-localized and functionally interdependent in producing natriuretic response. Hyperglycemic oxidative stress affecting sulfhydryl groups present a potential mechanism of such physical interaction between these receptors. (Support: R01DK061578)

Effect of hypophysectomy on energy balance and brown fat activity in obese Zucker rats

1988 ◽  
Vol 254 (2) ◽  
pp. E162-E166
Author(s):  
S. Holt ◽  
N. J. Rothwell ◽  
M. J. Stock ◽  
D. A. York
Keyword(s):  
Energy Balance ◽  
Binding Capacity ◽  
Zucker Rats ◽  
Bat Activity ◽  
Reduced Body ◽  
Brown Adipose ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Energy Gains ◽  
Pituitary Adrenal Axis

Hypophysectomy (HYPX) in genetically obese (fa/fa) Zucker rats significantly reduced body weight and energy gains and stimulated energy expenditure (by 34%), the thermic response to food (by 144%), and brown adipose tissue (BAT) mitochondrial GDP-binding capacity (by 190%) compared with pair-fed, sham-operated obese rats. These changes in energy balance in obese HYPX rats were reversed by corticosterone replacement (1 mg/day), but the increased BAT activity was only partly restored to normal. HYPX had only small effects on energy balance in lean Zucker rats compared with pair-fed, sham-operated lean controls but increased the acute thermic response to food and BAT mitochondrial GDP-binding capacity; these effects were inhibited by replacement of HYPX rats with corticosterone. The results suggest that alterations in the hypothalamic-pituitary-adrenal axis play a fundamental role in the development and maintenance of genetic obesity.

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