Cross-fostering does not alter the neurochemistry or behavior of spontaneously hypertensive rats

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Russell Vivienne A

2009-06-01

Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a highly heritable developmental disorder resulting from complex gene-gene and gene-environment interactions. The most widely used animal model, the spontaneously hypertensive rat (SHR, displays the major symptoms of ADHD (deficits in attention, impulsivity and hyperactivity and has a disturbance in the noradrenergic system when compared to control Wistar-Kyoto rats (WKY. The aim of the present study was to determine whether the ADHD-like characteristics of SHR were purely genetically determined or dependent on the gene-environment interaction provided by the SHR dam. Methods SHR/NCrl (Charles River, USA, WKY/NCrl (Charles River, USA and Sprague Dawley rats (SD/Hsd, Harlan, UK were bred at the University of Cape Town. Rat pups were cross-fostered on postnatal day 2 (PND 2. Control rats remained with their birth mothers to serve as a reference for their particular strain phenotype. Behavior in the open-field and the elevated-plus maze was assessed between PND 29 and 33. Two days later, rats were decapitated and glutamate-stimulated release of [3H]norepinephrine was determined in prefrontal cortex and hippocampal slices. Results There was no significant effect of "strain of dam" but there was a significant effect of "pup strain" on all parameters investigated. SHR pups travelled a greater distance in the open field, spent a longer period of time in the inner zone and entered the inner zone of the open-field more frequently than SD or WKY. SD were more active than WKY in the open-field. WKY took longer to enter the inner zone than SHR or SD. In the elevated-plus maze, SHR spent less time in the closed arms, more time in the open arms and entered the open arms more frequently than SD or WKY. There was no difference between WKY and SD behavior in the elevated-plus maze. SHR released significantly more [3H]norepinephrine in response to glutamate than SD or WKY in both hippocampus

Characteristics of arterial Na-K-ATPase in WKY and SHR

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Veit, E.I.; Cox, R.H.; Moisey, D.M.

1986-01-01

Segments of carotid and tail arteries and thoracic aorta from 12-week old male WKY and SHR were used to study Na-pump activity by 86 Rb-uptake method. Contiguous segments were used for the determination of cell Na content by ion substitution. The ouabain-dependence of maximum Na-pump activity was determined. The EC 50 value of ouabain (approximately 0.1 mM) was not significantly different for WKY and SHR arteries or at any of the three arterial sites. The maximum value of 86 Rb-uptake was significantly larger of all SHR arteries compared to WKY. No significant differences in ouabain-insensitive 86 Rb-uptake was found. No significant differences exist in estimates of cell Na in arteries from the two groups. Segments of arteries were stored in K-free PSS overnight at 2 0 C, and allowed to recover in normal PSS at 37 0 C for varying periods of time. Ouabain-sensitive 86 Rb-uptake and estimates of cell Na were determined during recovery from cold storage. There were no significant differences in the EC 50 value of Na, which produced a half-maximal ouabain-sensitive 86 Rb-uptake between WKY and SHR. The only difference observed in these studies was a larger turnover rate of the Na-pump in arteries from the SHR

Streptozotocin-induced diabetes mellitus in spontaneously hypertensive rats: a pathophysiological model for the combined effects of hypertension and diabetes

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Pijl, A. J.; van der Wal, A. C.; Mathy, M. J.; Kam, K. L.; Hendriks, M. G.; Pfaffendorf, M.; van Zwieten, P. A.

1994-01-01

The present study was undertaken to investigate the combined effects of hypertension and streptozotocin-induced diabetes mellitus in the rat. Accordingly, four groups of rats were studied: Wistar Kyoto rats (WKY), diabetic WKY, spontaneously hypertensive rats (SHR) and diabetic SHR, respectively.

Development of obesity in Zucker obese (fafa) rat in absence of hyperphagia.

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Cleary, M P; Vasselli, J R; Greenwood, M R

1980-03-01

The free-feeding, genetically obese rat is hyperphagic, hyperinsulinemic, and hypertriglyceridemic and has increased fat cell size and number compared to its lean littermate. These experiments demonstrate that, when fafa rats are prevented from expressing hyperphagia throughout life, the complete obese "syndrome" still develops. Furthermore, life-long food restriction does not prevent increased lipoprotein lipase in the fafa rat. The data support the concept that a peripheral metabolic adaptation, probably in lipid metabolism, results in preferential shunting of dietary substrate in the restricted obese rats to adipose tissue with concomitant decreases in other tissues.

Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

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Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

2010-04-01

This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p <0.05. Obese group on grain-based diet showed significant increase in MDA levels only in the duodenum, p <0.05. We conclude that dietary intervention differentially affects the oxidative markers in obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

Modification of the β-Adrenoceptor Stimulation Pathway in Zucker Obese and Obese Diabetic Rat Myocardium.

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Jiang, Cheng; Carillion, Aude; Na, Na; De Jong, Audrey; Feldman, Sarah; Lacorte, Jean-Marc; Bonnefont-Rousselot, Dominique; Riou, Bruno; Amour, Julien

2015-07-01

Although metabolic syndrome is associated with increased sympathetic activity that chronically stimulates β-adrenoceptors, the β-adrenoceptor signaling pathway has been poorly studied in this situation. We studied the β-adrenoceptor signaling pathway in Zucker lean, obese, and obese diabetic rats. Experimental, prospective study. University medical research laboratory. Adult male Zucker lean (control), obese, and obese diabetic rats. The effects of β-adrenoceptor stimulation were investigated in vitro in isolated left ventricular papillary muscles in control, obese, and obese diabetic rats. β1-, β2-, and β3-adrenoceptors and multidrug resistance-associated protein 4 were quantified by Western Blotting. Triglyceride, cholesterol, leptin, adiponectin, and C-peptide plasma concentrations were measured. Data are mean ± SD. Hyperlipidemia, high leptin, and C-peptide concentrations were observed in obese and obese diabetic strains, whereas hyperglycemia occurred only in the diabetic strain. The positive inotropic effect of isoproterenol was slightly reduced in obese rats (183% ± 11% of baseline; p = 0.003; n = 7) and markedly reduced in obese diabetic rats (137% ± 18% of baseline; p < 0.001; n = 10) when compared with control rats (210% ± 17% of baseline; n = 9). β1-adrenoceptors were down-regulated in obese (-41%; p = 0.02) and diabetic (-54%; p = 0.003) when compared with control rats, whereas β3-adrenoceptors and multidrug resistance-associated protein expression remained unchanged. Direct stimulation of adenylate cyclase with forskolin or administration of 3',5'-cyclic adenosine monophosphate suggests that subtle impairments also occurred beside the down-regulation of β1-adrenoceptor. The positive inotropic effect of β-adrenoceptor stimulation is slightly decreased in Zucker obese rats and was more markedly decreased in Zucker diabetic rats. These decreases are mainly related to β1-adrenoceptor down-regulation.

Ouabain binding to cultured vascular smooth muscle cells of the spontaneously hypertensive rat

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Hopp, L.; Khalil, F.; Tamura, H.; Kino, M.; Searle, B.M.; Tokushige, A.; Aviv, A.

1986-01-01

The binding of ouabain and K + to the Na + pump were analyzed in serially passed cultured vascular smooth muscle cells (VSMCs) originating from spontaneously hypertensive (SH) Wistar-Kyoto (WKY), and American Wistar (W) rats. The techniques have utilized analyses of displacement of [ 3 H]ouabain by both unlabeled ouabain and K + from specific binding sites on the VSMCs. The authors have found that 1) each of the VSMC preparations from the three rat strains appeared to demonstrate one population of specific ouabain receptors (Na + pumps); 2) the number of Na + pump units of both the SH and WKY rats was significantly lower than the number of Na + pump units of W rat VSMCs; 3) the equilibrium dissociation constant values (μM) for ouabain in VSMCs of SH and WKY rats were similar but were significantly higher than that of VSMCs derived from W rats; and 4) among the VSMCs originating from the three rat strains, the apparent equilibrium dissociation constant value for K + (mM) was the lowest in those of the SH rat compared with VSMCs of the WKY rat and W rat. Previous studies have demonstrated increased passive Na + and K + transport rate constants of SH rat VSMCs compared with either W or WKY rat cells. These findings suggest the possibility of higher permeabilities of the SH cells. They propose that the combined effect of a low number of Na + pump units with higher permeabilities to Na + and K + predisposes VSMCs of the SH rat to disturbances in their cellular ionic regulation. These genetic defects, if they occur in vivo, may lead to an increase in the vascular tone

Myocardial myostatin in spontaneously hypertensive rats with heart failure.

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Damatto, R L; Lima, A R R; Martinez, P F; Cezar, M D M; Okoshi, K; Okoshi, M P

2016-07-15

Myostatin has been shown to regulate skeletal and cardiac muscle growth. However, its status on long-term hypertrophied myocardium has not been addressed. The purpose of this study was to evaluate the expression of myocardial myostatin and its antagonist follistatin in spontaneously hypertensive rats (SHR) with heart failure. Eighteen-month-old SHR were evaluated to identify clinical features of heart failure such as tachypnea/labored respiration and weight loss. After heart failure was detected, rats were subjected to echocardiogram and euthanized. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as controls. Myostatin and follistatin protein expression was assessed by Western blotting. Statistical analysis was performed by Student's t test. All SHR (n=8) presented right ventricular hypertrophy and five had lung congestion. SHR had left chambers hypertrophy and dilation (left atrial diameter: WKY 5.73±0.59; SHR 7.28±1.17mm; p=0.004; left ventricular (LV) diastolic diameter/body weight ratio: WKY 19.6±3.1; SHR 27.7±4.7mm/kg; p=0.001), and LV systolic dysfunction (midwall fractional shortening: WKY 34.9±3.31; SHR 24.8±3.20%; p=0.003). Myocyte diameter (WKY 23.1±1.50, SHR 25.5±1.33μm; p=0.004) and myocardial interstitial collagen fraction (WKY 4.86±0.01; SHR 8.36±0.02%; pMyostatin (WKY 1.00±0.16; SHR 0.77±0.23 arbitrary units; p=0.035) and follistatin (WKY 1.00±0.35; SHR 0.49±0.18 arbitrary units; p=0.002) expression was lower in SHR. Myostatin and follistatin expression negatively correlated with LV diastolic diameter-to-body weight ratio and LV systolic diameter, and positively correlated with midwall fractional shortening. Myostatin and follistatin protein expression is reduced in the long-term hypertrophied myocardium from spontaneously hypertensive rats with heart failure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of psychotropic agents on extinction of lever-press avoidance in a rat model of anxiety vulnerability

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Xilu eJiao

2014-09-01

Full Text Available Avoidance and its perseveration represent key features of anxiety disorders. Both pharmacological and behavioral approaches (i.e. anxiolytics and extinction therapy have been utilized to modulate avoidance behavior in patients. However, the outcome has not always been desirable. Part of the reason is attributed to the diverse neuropathology of anxiety disorders. Here, we investigated the effect of psychotropic drugs that target various monoamine systems on extinction of avoidance behavior using lever-press avoidance task. Here we used the Wistar-Kyoto (WKY rat, a unique rat model that exhibits facilitated avoidance and extinction resistance along with malfunction of the dopamine (DA system. Sprague Dawley (SD and WKY rats were trained to acquire lever-press avoidance. WKY rats acquired avoidance faster and to a higher level compared to SD rats. During pharmacological treatment, bupropion, and desipramine significantly reduced avoidance response selectively in WKY rats. However, after the discontinuation of drug treatment, only those WKY rats that were previously treated with desipramine exhibited lower avoidance response compared to the control group. In contrast, none of the psychotropic drugs facilitated avoidance extinction in SD rats. Instead, desipramine impaired avoidance extinction and increased non-reinforced response in SD rats. Interestingly, paroxetine, a widely used antidepressant and anxiolytic, exhibited the weakest effect in WKY rats and no effects at all in SD rats. Thus, our data suggest that malfunctions in brain catecholamine system could be one of the underlying etiologies of anxiety-like behavior, particularly avoidance perseveration. Pharmacological manipulation targeting DA and norepinephrine is more effective to facilitate extinction learning in this strain. The data from the present study may shed light on new pharmacological approaches to treat patients with anxiety disorders who are not responding to serotonin re

Characteristics of central binding sites for [3H] DAMGO in spontaneously hypertensive rats

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Gulati, A.; Bhargava, H.N.

1990-01-01

The binding of [ 3 H] DAMGO, a highly selective ligand for μ-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. [ 3 H] DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B max value) and apparent dissociation constant (K d value) of [ 3 H] DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B max value of [ 3 H] DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K d values in the two strains did not differ. On the other hand, the B max value of [ 3 H] DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K d values in the two strains were similar

Self-administered nicotine differentially impacts body weight gain in obesity-prone and obesity-resistant rats.

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Rupprecht, Laura E; Smith, Tracy T; Donny, Eric C; Sved, Alan F

2017-07-01

Obesity and tobacco smoking represent the largest challenges to public health, but the causal relationship between nicotine and obesity is poorly understood. Nicotine suppresses body weight gain, a factor impacting smoking initiation and the failure to quit, particularly among obese smokers. The impact of nicotine on body weight regulation in obesity-prone and obesity-resistant populations consuming densely caloric diets is unknown. In the current experiment, body weight gain of adult male rats maintained on a high energy diet (31.8% kcal from fat) distributed into obesity-prone (OP), obesity-resistant (OR) and an intermediate group, which was placed on standard rodent chow (Chow). These rats were surgically implanted with intravenous catheters and allowed to self-administer nicotine (0 or 60μg/kg/infusion, a standard self-administration dose) in 1-h sessions for 20 consecutive days. Self-administered nicotine significantly suppressed body weight gain but not food intake in OP and Chow rats. Self-administered nicotine had no effect on body weight gain in OR rats. These data suggest that: 1) OR rats are also resistant to nicotine-induced suppression of body weight gain; and 2) nicotine may reduce levels of obesity in a subset of smokers prone to obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

Characteristics of central binding sites for ( sup 3 H) DAMGO in spontaneously hypertensive rats

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Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

1990-01-01

The binding of ({sup 3}H) DAMGO, a highly selective ligand for {mu}-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. ({sup 3}H) DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B{sub max} value) and apparent dissociation constant (K{sub d} value) of ({sup 3}H) DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B{sub max} value of ({sup 3}H) DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K{sub d} values in the two strains did not differ. On the other hand, the B{sub max} value of ({sup 3}H) DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K{sub d} values in the two strains were similar.

Moringa oleifera-rich diet and T cell calcium signaling in spontaneously hypertensive rats.

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Attakpa, E S; Bertin, G A; Chabi, N W; Ategbo, J-M; Seri, B; Khan, N A

2017-11-24

Moringa oleifera is a plant whose fruits, roots and leaves have been advocated for traditional medicinal uses. The physicochemical analysis shows that Moringa oleifera contains more dietary polyunsaturated fatty acids (PUFA) than saturated fatty acids (SFA). The consumption of an experimental diet enriched with Moringa oleifera extracts lowered blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats as compared to rats fed an unsupplemented control diet. Anti-CD3-stimulated T cell proliferation was diminished in both strains of rats fed the Moringa oleifera. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. Studies of platelets from patients with primary hypertension and from SHR support the notion that the concentration of intracellular free calcium [Ca(2+)](i) is modified in both clinical and experimental hypertension. We observed that the basal, [Ca(2+)](i) was lower in T cells of SHR than in those of WKY rats fed the control diet. Feeding the diet with Moringa oleifera extracts to WKY rats did not alter basal [Ca(2+)](i) in T cells but increased basal [Ca(2+)](i) in SHR. Our study clearly demonstrated that Moringa oleifera exerts antihypertensive effects by inhibiting the secretion of IL-2 and modulates T cell calcium signaling in hypertensive rats.

The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

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Lu-jing Chen

2014-01-01

Full Text Available Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood.

The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

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Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

2014-01-01

Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

Metabolic characteristics of skeletal muscle from lean and obese Zucker rats

International Nuclear Information System (INIS)

Campion, D.R.; Shapira, J.F.; Allen, C.E.; Hausman, G.J.; Martin, R.J.

1987-01-01

The purpose of this study was to determine if the metabolic response to obesity and to pair feeding of obese Zucker rats to lean Zucker rats was similar across skeletal muscles. Oxidation of glucose, palmitate and isoleucine was studied in muscle strips in vitro using appropriate 14- carbon substrates as tracers. The plantaris muscle was subjected to histochemical analyses using an alkaline actomyosin ATPase, NADH-tetrazolium reductase and an oil red 0 stain. Soleus muscles from both ad libitum and pair fed obese rats oxidized less glucose to CO 2 , but released similar amounts of lactate when compared to the soleus muscles of lean rats. Oxidation of glucose was similar in the extensor digitorum longus (EDL) muscle of ad libitum fed obese rats, but lower when pair fed to the intake of lean rats. No differences were apparent in palmitate oxidation to CO 2 or in incorporation into lipid, except in the EDL muscle of pair-fed obese rats which exhibited a higher rate for palmitate metabolism when compared with lean rats. Isoleucine oxidation to CO 2 was higher in the EDL and plantaris muscles, but similar in the soleus muscle of ad libitum-fed obese rats when compared with lean rats. The magnitude of the difference in isoleucine oxidation was similar when the obese rats were pair fed. No differences in the percentage of plantaris muscle fibers sensitive to alkaline ATPase staining were observed. The plantaris muscle of obese rats, contained a higher proportion of oxidative fibers. These results indicate the great risk in generalizing about metabolic activity of the whole skeletal muscle mass based on observations made on one, or even two, distinct muscles in this animal model. Also, pair feeding of obese to lean Zucker rats did not result in uniform change sin metabolism between muscles of the obese rats

Assessment of gut microbiota populations in lean and obese Zucker rats.

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Reza Hakkak

Full Text Available Obesity has been on the rise in the US and worldwide for the last several decades. Obesity has been associated with chronic disease development, such as certain types of cancer, type 2 diabetes, cardiovascular disease, and liver diseases. Previously, we reported that obesity promotes DMBA-induced mammary tumor development using the obese Zucker rat model. The intestinal microbiota is composed of a diverse population of obligate and facultative anaerobic microorganisms, and these organisms carry out a broad range of metabolic activities. Obesity has been linked to changes in the intestinal microbiota, but the composition of the bacterial populations in lean and obese Zucker rats has not been carefully studied. Therefore, the objective of this study was to determine the effects of obesity on the gut microbiota in this model. Lean and obese female Zucker rats (n = 16 were fed an AIN-93G-like diet for 8 weeks. Rats were weighed twice weekly, and fecal samples were collected at the beginning and end of the experiment. 16S rRNA gene sequencing was used to evaluate the composition of the fecal bacterial populations. At the outset of the study, the lean rats exhibited much lower ratios of the Firmicutes to Bacteroidetes phyla than the obese rats, but after 60 days, this ratio in the lean rats exceeded that of the obese. This shift was associated with reductions in the Bacteroidaceae, S24-7 and Paraprevotellaceae families in the lean rats. Obese rats also showed increased levels of the genus Akkermansia at day 60. PCoA plots of beta diversity showed clustering of the different test groups, indicating clear differences in intestinal microbiota populations associated with both the time point of the study and the lean or obese status in the Zucker rat model for obesity.

Avoidance Expression in Rats as a Function of Signal-Shock Interval: Strain and Sex Differences

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Richard J Servatius

2015-07-01

Full Text Available Inbred Wistar Kyoto (WKY rats express inhibited temperament, increased sensitivity to stress, and exaggerated expressions of avoidance. A long-standing observation for lever press escape/avoidance learning in rats is the duration of the warning signal (WS determines whether avoidance is expressed over escape. Outbred female Sprague-Dawley (SD rats trained with a 10-s WS efficiently escaped, but failed to exhibit avoidance; avoidance was exhibited to a high degree with WSs longer than 20-s. We examined this longstanding WS duration function and extended it to male SD and male and female WKY rats. A cross-over design with two WS durations (10 s or 60 s was employed. Rats were trained (20 trials/session in four phases: acquisition (10 sessions, extinction (10 sessions, re-acquisition (8 sessions and re-extinction (8 sessions. Consistent with the literature, female and male SD rats failed to express avoidance to an appreciable degree with a 10-s WS. When these rats were switched to a 60-s WS, performance levels in the initial session of training resembled the peak performance of rats trained with a 60-s WS. Therefore, the avoidance relationship was acquired, but not expressed at 10-s WS. Further, poor avoidance at 10-s does not adversely affect expression at 60-s. Failure to express avoidance with a 10-s WS likely reflects contrasting reinforcement value of avoidance, not a reduction in the amount of time available to respond or competing responses. In contrast, WKY rats exhibited robust avoidance with a 10-s WS, which was most apparent in female WKY rats. Exaggerated expression of avoidances by WKY rats, especially female rats, further confirms this inbred strain as a model of anxiety vulnerability.

Intermittent hypoxia in obese Zucker rats: cardiometabolic and inflammatory effects.

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Briançon-Marjollet, Anne; Monneret, Denis; Henri, Marion; Joyeux-Faure, Marie; Totoson, Perle; Cachot, Sandrine; Faure, Patrice; Godin-Ribuot, Diane

2016-11-01

What is the central question of this study? This study addresses the relative impact of obesity and intermittent hypoxia in the pathophysiological process of obstructive sleep apnoea by investigating the metabolic, inflammatory and cardiovascular consequences of intermittent hypoxia in lean and obese Zucker rats. What is the main finding and its importance? We found that obesity and intermittent hypoxia have mainly distinct consequences on the investigated inflammatory and cardiometabolic parameters in Zucker rats. This suggests that, for a given severity of sleep apnea, the association of obesity and obstructive sleep apnoea may not necessarily be deleterious. Obstructive sleep apnoea is associated with obesity with a high prevalence, and both co-morbidities are independent cardiovascular risk factors. Intermittent hypoxia (IH) is thought to be the main factor responsible for the obstructive sleep apnoea-related cardiometabolic alterations. The aim of this study was to assess the respective impact of obesity and IH on the inflammatory and cardiometabolic state in rats. Lean and obese Zucker rats were exposed to normoxia or chronic IH, and we assessed metabolic and inflammatory parameters, such as plasma lipids and glucose, serum leptin and adiponectin, liver cytokines, nuclear factor-κB activity and cardiac endothelin-1 levels. Myocardial infarct size was also evaluated following in vitro ischaemia-reperfusion. Circulating lipids, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin and adiponectin levels were higher in obese versus lean rats. Chronic IH did not have a significant impact on metabolic parameters in lean rats. In obese rats, IH increased glycaemia and HOMA-IR. Liver interleukin-6 and tumour necrosis factor-α levels were elevated in lean rats exposed to IH; obesity prevented the increase in interleukin-6 but not in tumour necrosis factor-α. Finally, IH exposure enhanced myocardial sensitivity to infarction in both lean and

Metabolic profile and genotoxicity in obese rats exposed to cigarette smoke.

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Damasceno, Debora C; Sinzato, Yuri K; Bueno, Aline; Dallaqua, Bruna; Lima, Paula H; Calderon, Iracema M P; Rudge, Marilza V C; Campos, Kleber E

2013-08-01

Experimental studies have shown that exposure to cigarette smoke has negative effects on lipid metabolism and oxidative stress status. Cigarette smoke exposure in nonpregnant and pregnant rats causes significant genotoxicity (DNA damage). However, no previous studies have directly evaluated the effects of obesity or the association between obesity and cigarette smoke exposure on genotoxicity. Therefore, the aim of the present investigation was to evaluate DNA damage levels, oxidative stress status and lipid profiles in obese Wistar rats exposed to cigarette smoke. Female rats subcutaneously (s.c.) received a monosodium glutamate solution or vehicle (control) during the neonatal period to induce obesity. The rats were randomly distributed into three experimental groups: control, obese exposed to filtered air, and obese exposed to tobacco cigarette smoke. After a 2-month exposure period, the rats were anesthetized and killed to obtain blood samples for genotoxicity, lipid profile, and oxidative stress status analyses. The obese rats exposed to tobacco cigarette smoke presented higher DNA damage, triglycerides, total cholesterol, free fatty acids, VLDL-c, HDL-c, and LDL-c levels compared to control and obese rats exposed to filtered air. Both obese groups showed reduced SOD activity. These results showed that cigarette smoke enhanced the effects of obesity. In conclusion, the association between obesity and cigarette smoke exposure exacerbated the genotoxicity, negatively impacted the biochemical profile and antioxidant defenses and caused early glucose intolerance. Thus, the changes caused by cigarette smoke exposure can trigger the earlier onset of metabolic disorders associated with obesity, such as diabetes and metabolic syndrome. Copyright © 2012 The Obesity Society.

Exercise training lowers the enhanced tonically active glutamatergic input to the rostral ventrolateral medulla in hypertensive rats.

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Zha, Yan-Ping; Wang, Yang-Kai; Deng, Yu; Zhang, Ru-Wen; Tan, Xing; Yuan, Wen-Jun; Deng, Xiao-Ming; Wang, Wei-Zhong

2013-04-01

It is well known that low-intensity exercise training (ExT) is beneficial to cardiovascular dysfunction in hypertension. The tonically active glutamatergic input to the rostral ventrolateral medulla (RVLM), a key region for control of blood pressure and sympathetic tone, has been demonstrated to be increased in hypertensive rats. The aim of this study was to determine the effect of ExT on the increased glutamatergic input to the RVLM in spontaneously hypertensive rat (SHR). Normotensive rats Wistar-Kyoto (WKY) and SHR were treadmill trained or remained sedentary (Sed) for 12 weeks and classed into four groups (WKY-Sed, WKY-ExT, SHR-Sed, and SHR-ExT). The release of glutamate in the RVLM and its contribution to cardiovascular activity were determined in WKY and SHR after treatment of ExT. Blood pressure and sympathetic tone were significantly reduced in SHR after treatment with ExT. Bilateral microinjection of the glutamate receptor antagonist kynurenic acid (2.7 nmol in 100 nL) into the RVLM significantly decreased resting blood pressure, heart rate, and renal sympathetic nerve activity in SHR-Sed but not in WKY groups (WKY-Sed and WKY-ExT). However, the degree of reduction in these cardiovascular parameters evoked by KYN was significantly blunted in SHR-ExT compared with SHR-Sed group. The concentration of glutamate and the protein expression of vesicular glutamate transporter 2 in the RVLM were significantly increased in SHR-Sed compared with WKY-Sed, whereas they were reduced after treatment with ExT. Our findings suggest that ExT attenuates the enhancement in the tonically acting glutamatergic input to the RVLM of hypertensive rats, thereby reducing the sympathetic hyperactivity and blood pressure. © 2013 Blackwell Publishing Ltd.

Role of phosphatidylinositol 3-kinase in angiotensin II regulation of norepinephrine neuromodulation in brain neurons of the spontaneously hypertensive rat.

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Yang, H; Raizada, M K

1999-04-01

Chronic stimulation of norepinephrine (NE) neuromodulation by angiotensin II (Ang II) involves activation of the Ras-Raf-MAP kinase signal transduction pathway in Wistar Kyoto (WKY) rat brain neurons. This pathway is only partially responsible for this heightened action of Ang II in the spontaneously hypertensive rat (SHR) brain neurons. In this study, we demonstrate that the MAP kinase-independent signaling pathway in the SHR neuron involves activation of PI3-kinase and protein kinase B (PKB/Akt). Ang II stimulated PI3-kinase activity in both WKY and SHR brain neurons and was accompanied by its translocation from the cytoplasmic to the nuclear compartment. Although the magnitude of stimulation by Ang II was comparable, the stimulation was more persistent in the SHR neuron compared with the WKY rat neuron. Inhibition of PI3-kinase had no significant effect in the WKY rat neuron. However, it caused a 40-50% attenuation of the Ang II-induced increase in norepinephrine transporter (NET) and tyrosine hydroxylase (TH) mRNAs and [3H]-NE uptake in the SHR neuron. In contrast, inhibition of MAP kinase completely attenuated Ang II stimulation of NET and TH mRNA levels in the WKY rat neuron, whereas it caused only a 45% decrease in the SHR neuron. However, an additive attenuation was observed when both kinases of the SHR neurons were inhibited. Ang II also stimulated PKB/Akt activity in both WKY and SHR neurons. This stimulation was 30% higher and lasted longer in the SHR neuron compared with the WKY rat neuron. In conclusion, these observations demonstrate an exclusive involvement of PI3-kinase-PKB-dependent signaling pathway in a heightened NE neuromodulatory action of Ang II in the SHR neuron. Thus, this study offers an excellent potential for the development of new therapies for the treatment of centrally mediated hypertension.

Central cardiovascular action of urotensin II in spontaneously hypertensive rats.

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Lin, Yingzi; Tsuchihashi, Takuya; Matsumura, Kiyoshi; Fukuhara, Masayo; Ohya, Yusuke; Fujii, Koji; Iida, Mitsuo

2003-10-01

We have previously reported that urotensin II acts on the central nervous system to increase blood pressure in normotensive rats. In the present study, we have determined the central cardiovascular action of urotensin II in spontaneously hypertensive rats (SHR). Intracerebroventricular (ICV) injection of urotensin II elicited a dose-dependent increase in blood pressure in both SHR and normotensive Wistar-Kyoto rats (WKY). The changes in mean arterial pressure induced by ICV urotensin II at doses of 1 and 10 nmol in the WKY were 8 +/- 2 and 23 +/- 3 mmHg, respectively. ICV administration of urotensin II caused significantly greater increases in blood pressure in SHR (16 +/- 3 mmHg at 1 nmol and 35 +/- 3 mmHg at 10 nmol, respectively) compared with those in WKY. Urotensin II (10 nmol) elicited significant and comparable increases in heart rate in SHR (107 +/- 10 bpm) and WKY (101 +/- 21 bpm). Plasma epinephrine concentrations after ICV administration of 10 nmol urotensin II were 203 +/- 58 pmol/ml in SHR and 227 +/- 47 pmol/ml in WKY, which tended to be higher than those in artificial cerebrospinal fluid-injected rats (73+/- 7 and 87 +/- 28 pmol/ml, respectively, p GPR 14 was expressed extensively in the glial cells within the brainstem, hypothalamus, and thalamus. These results suggest that central urotensin II may play a role in the pathogenesis of hypertension in SHR. Since GPR 14 was expressed in the glial cells of the brain, urotensin II may act as a neuromodulator to regulate blood pressure.

Alterations in substance P binding in brain nuclei of spontaneously hypertensive rats

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Shigematsu, K.; Niwa, M.; Kurihara, M.; Castren, E.; Saavedra, J.M.

1987-01-01

Substance P binding sites were characterized in brain nuclei of young (4-wk-old) and adult (16-wk-old) spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats by quantitative autoradiography. Young SHR presented higher affinity constants (K/sub A/) than young WKY. The changes were restricted to locus coeruleus, the area postrema, the dorsal motor nucleus of the vagus, and to discrete areas located in lobes 9 and 10 of the vermis cerebelli of SHR. There were no differences in the maximal binding capacity (B/sub max/) except in the nucleus ambiguus where the B/sub max/ was lower than WKY. Conversely, the number of substance P binding sites was higher in the locus coeruleus, the nucleus tegmentalis dorsalis, the nucleus ambiguus, the dorsal motor nucleus of the vagus, the hypoglossal nucleus, the inferior olivary nucleus, and lobes 9 and 10 of the vermis cerebelli of adult SHR when compared with adult WKY. The results support the hypothesis of a role for brain substance P in blood pressure regulation and in genetic hypertension in rats

Regulation of lipid synthesis in hepatocytes from lean and obese Zucker rats

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Triscari, J.; Greenwood, M.R.; Sullivan, A.C.

1981-01-01

Fatty acid synthesis and CO 2 production were evaluated in hepatocytes from lean and obese Zucker rats in the presence of 3 H 2 O, and several carbon precursors. The incorporation of 3 H 2 O into fatty acids was greater in obese compared to lean rats in both the isolated hepatocyte and in vivo. The rates of incorporation of 3 H 2 O into fatty acids and cholesterol in hepatocytes of both lean and obese rats were linear for 2 hr, in the absence or presence of 16.7 mM glucose. Rates of fatty acid synthesis were higher in the presence of 16.7 mM glucose compared to the absence of glucose in both lean and obese while rates of cholesterol synthesis were similar. The incorporation of 3H2O into fatty acids, but not into cholesterol, was correlated with increasing glucose concentration and was 2 to three-fold higher in hepatocytes of obese compared to lean rats in the presence of several carbon precursors. Differences in CO 2 production between lean and obese rats suggested increased pentose phosphate shunt activity, decreased pyruvate dehydrogenase activity, and lower tricarboxylic acid cycle activity in obese rats. Fatty acid synthesis and CO 2 production from 3 H 2 O and [U- 14 C]glucose in hepatocytes of lean and obese rats was similarly elevated by insulin and depressed by glucagon at several concentrations, suggesting that hepatocytes of obese animals respond to these hormones. These data indicate that rates of hepatic fatty acid synthesis although higher in obese rats respond to modulation in a fashion which is similar to the response in lean rats. The present studies suggest that the oxidation of several carbon precursors in the tricarboxylic acid cycle is diminished in obese compared to lean rats, but pentose phosphate shunt activity is greater in the obese Zucker rats

Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

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Kyeremanteng, C; MacKay, J C; James, J S; Kent, P; Cayer, C; Anisman, H; Merali, Z

2014-10-03

Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT. Copyright © 2014 Elsevier Inc. All rights reserved.

Time course of training-induced microcirculatory changes and of vegf expression in skeletal muscles of spontaneously hypertensive female rats

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S.L. Amaral

2008-05-01

Full Text Available Exercise-induced vessel changes modulate arterial pressure (AP in male spontaneously hypertensive rats (SHR. Vascular endothelial growth factor (VEGF is important for angiogenesis of skeletal muscle. The present study evaluated the time course of VEGF and angiogenesis after short- and long-term exercise training of female SHR and Wistar Kyoto (WKY rats, 8-9 weeks (200-250 g. Rats were allocated to daily training or remained sedentary for 3 days (N = 23 or 13 weeks (N = 23. After training, the carotid artery was catheterized for AP measurements. Locomotor (tibialis anterior and gracilis and non-locomotor skeletal muscles (temporalis were harvested and prepared for histologic and protein expression analyses. Training increased treadmill performance by all groups (SHR = 28%, WKY = 64%, 3 days and (SHR = 141%, WKY = 122%, 13 weeks. SHR had higher values of AP than WKY (174 ± 4 vs 111 ± 2 mmHg that were not altered by training. Three days of running increased VEGF expression (SHR = 28%, WKY = 36% simultaneously with an increase in capillary-to-fiber ratio in gracilis muscle (SHR = 19%, WKY = 15%. In contrast, 13 weeks of training increased gracilis capillary-to-fiber ratio (SHR = 18%, WKY = 19%, without simultaneous changes in VEGF expression. Training did not change VEGF expression and capillarity of temporalis muscle. We conclude that training stimulates time- and tissue-dependent VEGF protein expression, independent of pressure levels. VEGF triggers angiogenesis in locomotor skeletal muscle shortly after the exercise starts, but is not involved in the maintenance of capillarity after long-term exercise in female rats.

Ketamine facilitates extinction of avoidance behavior and enhances synaptic plasticity in a rat model of anxiety vulnerability: Implications for the pathophysiology and treatment of anxiety disorders.

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Fortress, Ashley M; Smith, Ian M; Pang, Kevin C H

2018-05-08

Anxiety disorders and posttraumatic stress disorder (PTSD) share a common feature of pathological avoidance behavior. The Wistar Kyoto (WKY) rat has been used as a model of anxiety vulnerability, expressing a behaviorally inhibited temperament, acquiring avoidance behavior more rapidly and displaying extinction-resistant avoidance compared to Sprague Dawley (SD) rats. Subanesthetic levels of ketamine have gained attention as a rapid antidepressant in treatment-resistant depression. While traditional antidepressants are commonly used to treat anxiety disorders and PTSD, the therapeutic utility of ketamine for these disorders is much less understood. The hippocampus is critical for the actions of antidepressants, is a structure of implicated in anxiety disorders and PTSD, and is necessary for extinction of avoidance in SD rats. WKY rats have impaired hippocampal long-term potentiation (LTP), suggesting that persistent avoidance in WKY rats may be due to deficient hippocampal synaptic plasticity. In the present study, we hypothesized that ketamine would facilitate extinction of avoidance learning in WKY rats, and do so by enhancing hippocampal synaptic plasticity. As predicted, ketamine facilitated extinction of avoidance behavior in a subset of WKY rats (responders), with effects lasting at least three weeks. Additionally, LTP in these rats was enhanced by ketamine. Ketamine was not effective in facilitating avoidance extinction or in modifying LTP in WKY non-responders. The results suggest that subanesthetic levels of ketamine may be useful for treating anxiety disorders by reducing avoidance behaviors when combined with extinction conditions. Moreover, ketamine may have its long-lasting behavioral effects through enhancing hippocampal synaptic plasticity. Copyright © 2018. Published by Elsevier Ltd.

Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats

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Jennifer L. Cornish

2012-09-01

Full Text Available The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®. With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY rats and in Spontaneously Hypertensive Rats (SHR, a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day or distilled water (dH2O. The effect of chronic treatment on delayed reinforcement tasks (DRT and tyrosine hydroxylase immunoreactivity (TH-ir in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in “normal” WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.

Rats

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Alexey Kondrashov

2012-01-01

Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

The physiological response of obese rat model with rambutan peel extract treatment

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Sri Rahayu Lestari

2014-09-01

Full Text Available Objective: To determine body weight gain, expression of Igf-1 and Igf-1 receptor on obese rat model treated with rambutan peel extract (RPE as a physiological response. Methods: Normal and obese rat feed with normal and high calorie diet around 1 2 weeks and continued to treat with ellagic acid, RPE 15, 30 and 60 mg/kg body weight respectively. Physiological responses observed were weight gain and expression of Igf-1 with its receptor. Body weight of rat was weighed once per week. Expression of Igf-1 and igf-1R observed with fluorescence immunohistochemistry. The intensity of Igf-1 and Igf-1R expression was analysis using FSX-BSW software. Results: The lowest weight gain was obtained on obese rat model treated with RPE 30 mg/kg body weight. The expression of Igf-1 and Igf-1R were reduced on obese rat model treated with RPE compared with obese rat model of non treatment (P<0.05. The low expression of Igf-1 and Igf-1R was found on obese rat model treated with ellagic acid and RPE 30 mg/kg body weight. Conclusions: The RPE was effecting to the physiological response on obese rat model. The RPE 30 mg/kg body weight inhibited body weight gain and decreased the expression of Igf-1 and Igf- 1R of obese rat model.

Decreased α1-adrenergic receptor-mediated inositide hydrolysis in neurons from hypertensive rat brain

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Feldstein, J.B.; Gonzales, R.A.; Baker, S.P.; Sumners, C.; Crews, F.T.; Raizada, M.K.

1986-01-01

The expression of α 1 -adrenergic receptors and norepinephrine (NE)-stimulated hydrolysis of inositol phospholipid has been studied in neuronal cultures from the brains of normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SH) rats. Binding of 125 I-1-[β-(4-hydroxyphenyl)-ethyl-aminomethyl] tetralone (HEAT) to neuronal membranes was 68-85% specific and was rapid. Competition-inhibition experiments with various agonists and antagonists suggested that 125 I-HEAT bound selectively to α 1 -adrenergic receptors. Specific binding of 125 I-HEAT to neuronal membranes from SH rat brain cultures was 30-45% higher compared with binding in WKY normotensive controls. This increase was attributed to an increase in the number of α 1 -adrenergic receptors on SH rat brain neurons. Incubation of neuronal cultures of rat brain from both strains with NE resulted in a concentration-dependent stimulation of release of inositol phosphates, although neurons from SH rat brains were 40% less responsive compared with WKY controls. The decrease in responsiveness of SH rat brain neurons to NE, even though the α 1 -adrenergic receptors are increased, does not appear to be due to a general defect in membrane receptors and postreceptor signal transduction mechanisms. This is because neither the number of muscarinic-cholinergic receptors nor the carbachol-stimulated release of inositol phosphates is different in neuronal cultures from the brains of SH rats compared with neuronal cultures from the brains of WKY rats. These observations suggest that the increased expression of α 1 -adrenergic receptors does not parallel the receptor-mediated inositol phosphate hydrolysis in neuronal cultures from SH rat brain

Diet composition determines course of hyperphagia in developing Zucker obese rats.

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Vasselli, J R; Maggio, C A

1990-12-01

Previous observations from this laboratory indicate that, during growth, the hyperphagia of the male genetically obese Zucker rat reaches a peak or "breakpoint" and then declines. To examine the effect of dietary macronutrient content on the course of hyperphagia, groups of male lean and obese rats were maintained from 5-28 weeks of age on powdered chow, or isocaloric diets (3.6 kcal/g) containing 72% of calories as corn oil, dextrose, or soy isolate protein (n = 5 lean and obese rats/diet). On chow, hyperphagia was maintained at a level of 7-8 g above lean control intake until a "breakpoint" was reached at 17 weeks, and obese intake declined to lean control level. On the fat diet, hyperphagia was increased to 10 g/day when a breakpoint was reached at 8 weeks. On the dextrose and protein diets, hyperphagia at a level of 3-4 g/day reached breakpoints at weeks 18 and 16, respectively. On all diets, the intakes of obese rats were precisely equal to the intakes of lean control rats by weeks 19-20. These data show that the magnitude and duration of hyperphagia in the developing obese rat are influenced by diet composition. Previously, we have proposed that the obese rat's hyperphagia arises from rapid adipocyte filling. Since high-fat diets facilitate adipocyte enlargement, the early "breakpoint" of hyperphagia seen with the high-fat diet may indicate that this feeding stimulation decreases as the fat cells of the obese rat approach maximal size.

The role of the sympathetic nervous system in radiation-induced apoptosis in jejunal crypt cells of spontaneously hypertensive rats

International Nuclear Information System (INIS)

Matsuu, Mutsumi; Shichijo; Kazuko; Nakamura, Yasuko; Ikeda, Yuji; Naito, Shinji; Ito, Masahiro; Okaichi, Kumio; Sekine, Ichiro

2000-01-01

To evaluate the effect of the sympathetic nervous system on radiation-induced apoptosis in jejunal crypt cells, apoptosis levels were compared in spontaneously hypertensive rats (SHR), animals which are a genetic hyperfunction model of the sympathetic nervous system, and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were exposed to whole body X-ray irradiation at doses from 0.5 to 2 Gy. The apoptotic index in jejunal crypt cells was significantly greater in SHR than in WKY at each time point after irradiation and at each dose. WKY and SHR were treated with reserpine to induce sympathetic dysfunction, and were subsequently exposed to irradiation. Reserpine administration to SHR or WKY resulted in a significant suppression of apoptosis. p53 accumulation was detected in the jejunum in both WKY and SHR after irradiation by Western blotting analysis. There were no significant differences in the levels of p53 accumulation in irradiated intestine between WKY and SHR. These findings suggested that hyperfunction of the sympathetic nervous system is involved in the mechanism of high susceptibility to radiation-induced apoptosis of the jejunal crypt cells. (author)

Role of the collecting duct in the exaggerated natriuresis of spontaneously hypertensive rats

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Francisco, L.L.; DiBona, G.F.

1980-01-01

To carry out a comparative examination of exaggerated natriumresis in the kidneys with essential hypertonia, 2 rat populations consisting of 11 spontaneously hypertensive rats (SHR) and, for controlling, 9 Wistar Kyoto rats (WKY), were chosen. In rats of the same age and weight, there was a significant arterial difference in the blood pressure. After the intravenous administration of isotonic NaCl, the urinary flow rate and sodium excretion are increased. The end-distal tubule-microinjection showed the 14 C-inulin recovery while that of 22 Na was significantly higher in SHR than in WKY. (APR) [de

The Effects of Methylphenidate on Goal-Directed Behavior in a Rat Model of ADHD

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Joman Y. Natsheh

2015-11-01

Full Text Available Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75-P105] Spontaneously Hypertensive Rats (SHR (ADHD rat model and Wistar-Kyoto rats (WKY, the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action-outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate, a commonly used ADHD medication, on goal-directed behavior, we injected rats with either Methylphenidate or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, methylphenidate administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how methylphenidate acts differently on SHR and WKY animals to restore or impair this behavior, respectively.

The metabolic clearance rate of corticosterone in lean and obese male Zucker rats

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White, B.D.; Corll, C.B.; Porter, J.R.

1989-01-01

The obese Zucker rat is an animal model of human juvenile-onset obesity. These rats exhibit numerous endocrine and metabolic abnormalities. Adrenalectomy of obese rats has been shown to reduce or reverse several of these abnormalities, thereby implying that corticosterone may contribute to the expression of obesity in this animal. Furthermore, it has been shown that the circadian rhythm of plasma corticosterone is disturbed in obese Zucker rats resulting in elevated morning plasma corticosterone concentrations in obese rats as compared to lean rats. In a effort to better elucidate the mechanism of the elevated morning levels of plasma corticosterone, the metabolic clearance rate of corticosterone was determined in the morning for lean and obese male Zucker rats (12 to 20 weeks). Additionally, the biliary and urinary excretion of labeled corticosterone and/or its metabolites were determined. The metabolic clearance rate of corticosterone was significantly greater in obese rats than in their lean counterparts. Both the metabolic clearance rate and the volume of compartments significantly correlated with body weight. No correlation was found between body weight and the elimination rate constant. The increased metabolic clearance rate of obese rats appeared to be due to an increase in the physiologic distribution of corticosterone and not to an alteration in the enzymes responsible for corticosterone metabolism. It appears that the metabolic clearance rate of corticosterone in obese Zucker rats does not contribute to elevated morning concentrations of plasma corticosterone previously observed in these animals. It suggests that the adrenal corticosterone secretion rate must actually be greater than one would expect from the plasma corticosterone concentrations alone

Effects of taurine on resting-state fMRI activity in spontaneously hypertensive rats.

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Chen, Vincent Chin-Hung; Hsu, Tsai-Ching; Chen, Li-Jeng; Chou, Hong-Chun; Weng, Jun-Cheng; Tzang, Bor-Show

2017-01-01

Attention deficit hyperactivity disorder (ADHD) is a global behavior illness among children and adults. To investigate the effects of taurine on resting-state fMRI activity in ADHD, a spontaneously hypertensive rat (SHR) animal model was adopted. Significantly decreased serum C-reactive protein (CRP) was detected in rats of Wistar Kyoto (WKY) high-taurine group and significantly decreased interleukin (IL)-1β and CRP were detected in rats of SHR low-taurine and high-taurine groups. Moreover, significantly higher horizontal locomotion was detected in rats of WKY low-taurine and SHR low-taurine groups than in those of controls. In contrast, significantly lower horizontal locomotion was detected in rats of the SHR high-taurine group than in those of the SHR control group. Additionally, significantly lower functional connectivity (FC) and mean amplitude of low-frequency fluctuation (mALFF) in the bilateral hippocampus in rats of WKY high-taurine and SHR high-taurine groups was detected. Notably, the mALFF in rats of the SHR low-taurine and high-taurine groups was significantly lower than in those of the SHR control group. These findings suggest that the administration of a high-dose taurine probably improves hyperactive behavior in SHR rats by ameliorating the inflammatory cytokines and modulating brain functional signals in SHR rats.

Learned helplessness and social avoidance in the Wistar-Kyoto rat.

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Nam, Hyungwoo; Clinton, Sarah M; Jackson, Nateka L; Kerman, Ilan A

2014-01-01

The Wistar-Kyoto (WKY) rat is an established depression model characterized by elevated anxiety- and depression-like behavior across a variety of tests. Here we further characterized specific behavioral and functional domains relevant to depression that are altered in WKY rats. Moreover, since early-life experience potently shapes emotional behavior, we also determined whether aspects of WKYs' phenotype were modifiable by early-life factors using neonatal handling or maternal separation. We first compared WKYs' behavior to that of Sprague-Dawley (SD), Wistar, and Spontaneously Hypertensive (SHR) rats in: the open field test, elevated plus maze, novelty-suppressed feeding test, a social interaction test, and the forced swim test (FST). WKYs exhibited high baseline immobility in the FST and were the only strain to show increased immobility on FST Day 2 vs. Day 1 (an indicator of learned helplessness). WKYs also showed greater social avoidance, along with enlarged adrenal glands and hearts relative to other strains. We next tested whether neonatal handling or early-life maternal separation stress influenced WKYs' behavior. Neither manipulation affected their anxiety- and depressive-like behaviors, likely due to a strong genetic underpinning of their phenotype. Our findings indicate that WKY rats are a useful model that captures specific functional domains relevant to clinical depression including: psychomotor retardation, behavioral inhibition, learned helplessness, social withdrawal, and physiological dysfunction. WKY rats appear to be resistant to early-life manipulations (i.e., neonatal handling) that are therapeutic in other strains, and may be a useful model for the development of personalized anti-depressant therapies for treatment resistant depression.

Learned helplessness and social avoidance in the Wistar-Kyoto rat

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Hyungwoo eNam

2014-04-01

Full Text Available The Wistar-Kyoto (WKY rat is an established depression model characterized by elevated anxiety- and depression-like behavior across a variety of tests. Here we further characterized specific behavioral and functional domains relevant to depression that are altered in WKY rats. Moreover, since early-life experience potently shapes emotional behavior, we also determined whether aspects of WKYs’ phenotype were modifiable by early-life factors using neonatal handling or maternal separation. We first compared WKYs’ behavior to that of Sprague-Dawley (SD, Wistar, and Spontaneously Hypertensive (SHR rats in: the open field test, elevated plus maze, novelty-suppressed feeding test, a social interaction test, and the forced swim test (FST. WKYs exhibited high baseline immobility in the FST and were the only strain to show increased immobility on FST Day 2 vs. Day 1 (an indicator of learned helplessness. WKYs also showed greater social avoidance, along with enlarged adrenal glands and hearts relative to other strains. We next tested whether neonatal handling or early-life maternal separation stress influenced WKYs’ behavior. Neither manipulation affected their anxiety- and depressive-like behaviors, likely due to a strong genetic underpinning of their phenotype. Our findings indicate that WKY rats are a useful model that captures specific functional domains relevant to clinical depression including: psychomotor retardation, behavioral inhibition, learned helplessness, social withdrawal, and physiological dysfunction. WKY rats appear to be resistant to early-life manipulations (i.e. neonatal handling that are therapeutic in other strains, and may be a useful model for the development of personalized anti-depressant therapies for treatment resistant depression.

LONG TERM EFFECT OF CHROMIUM ON LIPID PROFILE AND SOME HORMONES IN OBESE RATS

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GABR, S.A.; ABDEL-KHALEK, L.G.; GHAREIB, S.A.

2008-01-01

In the present study, the long term effect of chromium picolinate (intake 30 and 60 days) on lipid profile, testosterone, thyroid hormones, corticosterone and insulin was studied in obese male rats. A total of 48 male albino rats were arranged into four equal groups. The rats were distributed into four equal main groups: 1- Normal rats left without any treatment and served as a control group. 2- Normal rats treated with chromium picolinate at a dose of 40 μg/kg/day. 3-Obese rats (after the induction of obesity) using fed high fat diet. 4- Obese rats treated with chromium picolinate. The results obtained showed that normal rats treated with chromium picolinate for 30 or 60 days had no changes in total cholesterol, triglycerides, total lipids, LDL-cholesterol, HDL-cholesterol, triiodothyronine (T 3 ) and thyroxine (T 4 ) when compared with the control group. The testosterone and corticosterone levels were significantly decreased in rats treated with chromium picolinate for 60 days. Insulin level was significantly increased in treated rats for 60 days when compared with the control ones. In obese rats, the lipid profile and corticosterone were significantly increased at 30 and 60 days, while the insulin levels were increased in obese rats fed on high fat diet for 30 days as compared with the control rats. The administration of chromium picolinate to obese rats succeeded to decrease the lipid profile, corticosterone (at 60 days) and insuline (at 30 days) when compared with the obese rats. It could be concluded from this study that chromium picolinate possess beneficial effects in decreasing lipid profile in obese rats. Therefore, additional of chromium picolinate may be useful in obese rats to burn excess body fat and in treatment of hypercholesterolemia. Since it cause decrease in testosterone level, its use was advised to restrict to relatively old age

Obesity-resistant S5B rats showed great cocaine conditioned place preference than the obesity-prone OM rats

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Thanos, P.K.; Wang, G.; Thanos, P.K..; Kim, R.; Cho, J.; Michaelides, M.; Anderson, B.J.; Primeaux, S.D.; Bray, G.A.; Wang, G.-J.; Robinson, J.K.; Volkow, N.D.

2010-12-01

Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and conditioned responses to food and drug rewards. Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet. We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP). To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity, we then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains. OM and S5B/P rats were conditioned with cocaine (5 or 10 mg/kg) in one chamber and saline in another for 8 days. Rats were then tested for cocaine preference. The effects of BC (0.5, 1, 5, 10, 20 mg/kg) on cocaine preference were then assessed in subsequent test sessions. OM rats did not show a significant preference for the cocaine-paired chamber on test day. Only the S5B/P rats showed cocaine CPP. Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5 mg/kg cocaine and in OM rats treated with 10 mg/kg cocaine. Our results indicated that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats. These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine). However, they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs.

Absence of “Warm-Up” during Active Avoidance Learning in a Rat Model of Anxiety Vulnerability: Insights from Computational Modeling

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Myers, Catherine E.; Smith, Ian M.; Servatius, Richard J.; Beck, Kevin D.

2014-01-01

Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL) models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of lever-press avoidance learning in Sprague-Dawley (SD) rats and in the inbred Wistar Kyoto (WKY) rat, which has been proposed as a model of anxiety vulnerability. We focus on “warm-up,” transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the “standard” inter-session interval is shortened from 48 to 24 h, SD rats (but not WKY) will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes. PMID

Genetic Regulation of Development of Thymic Lymphomas Induced by N‐Propyl‐N‐nitrosourea in the Rat

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Fukami, Hiroko; Nishimura, Mayumi; Matsuyama, Mutsushi

1995-01-01

To clarify the linkage between Hbb and Tls‐1 (thymic lymphoma susceptible‐1) loci and to investigate other loci concerned in thymic lymphomagenesis, the BUF/Mna rat, which is highly sensitive to the lymphomagenic activity of N‐propyl‐N‐nitrosourea (PNU), the WKY/NCrj rat, reported to be resistant, and their cross offspring were subjected to genetic analysis. F1 hybrid and backcross generations were raised from the 2 strains, and 6 genetic markers including Hbb were analyzed in individuals of the backcross generation. However, no linkage between Hbb and Tls‐1 loci could be demonstrated since WKY rats also developed a high incidence of thymic lymphomas in response to PNU. Nevertheless, thymic lymphomas developed more rapidly and reached a larger size in the BUF rats. F1 rats expressed a rather rapid and large tumor growth phenotype, while the [(WKY × BUF) × WKY] backcross generation consisted of rats with either rapidly growing or slowly growing tumors. It was thus concluded that rapid development of thymic lymphomas is determined by a gene, provisionally designated Tls‐3. Analysis of the relationship between 6 genetic markers and development of thymic lymphoma in the backcross generation demonstrated that the Tls‐3 locus is loosely linked to the Gc locus, suggesting a possible location on rat chromosome 14. Tls‐3 may not be identical with Tls‐1 and other genes known to be relevant to thymic tumors, but its relationship with Tls‐2 remains obscure. PMID:7559080

Differential Secretion of Satiety Hormones With Progression of Obesity in JCR: LA-corpulent Rats

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Parnell, Jill A.; Reimer, Raylene A.

2013-01-01

Objective To characterize the gastrointestinal tract at the onset and in well-established obesity. Methods and Procedures Lean (+/?) and obese (cp/cp) male JCR:LA-cp rats lacking a functional leptin receptor were killed at 3.5 weeks and 9 months of age and plasma concentrations of satiety hormones determined. The small intestine, colon, and stomach were measured, weighed, and mRNA levels of satiety genes quantified. Results At the onset of obesity, obese rats had greater intestine, colon, and liver mass when adjusted for body weight compared to lean rats. Conversely, adult rats with established obesity had lower intestine and colon mass and length after adjustment for body weight. Early changes in gene expression included decreased ghrelin mRNA levels in stomach and increased peptide YY (PYY) mRNA levels in duodenum of young obese rats. After massive accumulation of adipose tissue had occurred, adult obese rats had increased proglucagon and ghrelin mRNA expression in the proximal intestine. In the distal small intestine, obese rats had lower proglucagon, ghrelin, and PYY mRNA levels. Finally, at the onset and in well-established obesity, obese rats had higher plasma insulin, amylin, glucagon like peptide-1 (GLP-1), and PYY, a finding, with the exception of insulin, unique to this model. Plasma total ghrelin levels were significantly lower at the onset of obesity and established obesity compared to the lean rats. Discussion Several defects are manifested in the obese gut early on in the disease before the accumulation of large excesses of body fat and represent potential targets for early intervention in obesity. PMID:18239578

[MK-801 or DNQX reduces electroconvulsive shock-induced impairment of learning-memory and hyperphosphorylation of Tau in rats].

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Liu, Chao; Min, Su; Wei, Ke; Liu, Dong; Dong, Jun; Luo, Jie; Liu, Xiao-Bin

2012-08-25

This study explored the effect of the excitatory amino acid receptor antagonists on the impairment of learning-memory and the hyperphosphorylation of Tau protein induced by electroconvulsive shock (ECT) in depressed rats, in order to provide experimental evidence for the study on neuropsychological mechanisms improving learning and memory impairment and the clinical intervention treatment. The analysis of variance of factorial design set up two intervention factors which were the electroconvulsive shock (two level: no disposition; a course of ECT) and the excitatory amino acid receptor antagonists (three level: iv saline; iv NMDA receptor antagonist MK-801; iv AMPA receptor antagonist DNQX). Forty-eight adult Wistar-Kyoto (WKY) rats (an animal model for depressive behavior) were randomly divided into six experimental groups (n = 8 in each group): saline (iv 2 mL saline through the tail veins of WKY rats ); MK-801 (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats) ; DNQX (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats ); saline + ECT (iv 2 mL saline through the tail veins of WKY rats and giving a course of ECT); MK-801 + ECT (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats and giving a course of ECT); DNQX + ECT (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats and giving a course of ECT). The Morris water maze test started within 1 day after the finish of the course of ECT to evaluate learning and memory. The hippocampus was removed from rats within 1 day after the finish of Morris water maze test. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The contents of Tau protein which included Tau5 (total Tau protein), p-PHF1(Ser396/404), p-AT8(Ser199/202) and p-12E8(Ser262) in the hippocampus of rats were detected by immunohistochemistry staining (SP) and Western blot. The results showed that ECT and the glutamate ionic receptor blockers (NMDA receptor antagonist MK-801 and

Pharmacokinetics of tritiated water in normal and dietary-induced obese rats

International Nuclear Information System (INIS)

Shum, L.Y.; Jusko, W.J.

1986-01-01

Tritiated water disposition was characterized in normal and dietary-induced obese rats to assess pharmacokinetic concerns in calculating water space and estimating body fat. A monoexponential decline in serum tritium activity was observed in both groups of rats, thus facilitating use of various computational methods. The volume of distribution and the total clearance of tritium in obese rats were larger than in normal rats because of the increased body weight. The values of water space (volume of distribution) estimated from moment analysis or dose divided by serum tritium activity at time zero (extrapolated) or at 2 hr were all similar. Thus, obesity does not alter the distribution equilibrium time and distribution pattern of tritium, and the conventional 2-hr single blood sampling after intravenous injection is adequate to estimate the water space of normal and obese rats

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

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Vasselli, J R; Fiene, J A; Maggio, C A

1992-01-01

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.

Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

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Rahmani, N.H.; Gulati, A.; Bhargava, H.N.

1991-01-01

The binding of 3 H-naltrexone, an opiate receptor antagonist, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. 3 H-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of 3 H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B max value) and apparent dissociation constant (K d value) values of 3 H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midgrain, cortex and spinal cord of WKY and SHR rates did not differ. The B max value of 3 H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K d values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with 3 H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats

Impaired Sympathoadrenal Axis Function Contributes to Enhanced Insulin Secretion in Prediabetic Obese Rats

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Ana Eliza Andreazzi

2011-01-01

Full Text Available The involvement of sympathoadrenal axis activity in obesity onset was investigated using the experimental model of treating neonatal rats with monosodium L-glutamate. To access general sympathetic nervous system activity, we recorded the firing rates of sympathetic superior cervical ganglion nerves in animals. Catecholamine content and secretion from isolated adrenal medulla were measured. Intravenous glucose tolerance test was performed, and isolated pancreatic islets were stimulated with glucose and adrenergic agonists. The nerve firing rate of obese rats was decreased compared to the rate for lean rats. Basal catecholamine secretion decreased whereas catecholamine secretion induced by carbachol, elevated extracellular potassium, and caffeine in the isolated adrenal medulla were all increased in obese rats compared to control. Both glucose intolerance and hyperinsulinaemia were observed in obese rats. Adrenaline strongly inhibited glucose-induced insulin secretion in obese animals. These findings suggest that low sympathoadrenal activity contributes to impaired glycaemic control in prediabetic obese rats.

N-Acetylcysteine Prevents Hypertension via Regulation of the ADMA-DDAH Pathway in Young Spontaneously Hypertensive Rats

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Nai-Chia Fan

2013-01-01

Full Text Available Asymmetric dimethylarginine (ADMA reduces nitric oxide (NO, thus causing hypertension. ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH, which can be inhibited by oxidative stress. N-Acetylcysteine (NAC, an antioxidant, can facilitate glutathione (GSH synthesis. We aimed to determine whether NAC can prevent hypertension by regulating the ADMA-DDAH pathway in spontaneously hypertensive rats (SHR. Rats aged 4 weeks were assigned into 3 groups (n=8/group: control Wistar Kyoto rats (WKY, SHR, and SHR receiving 2% NAC in drinking water. All rats were sacrificed at 12 weeks of age. SHR had higher blood pressure than WKY, whereas NAC-treated animals did not. SHR had elevated plasma ADMA levels, which was prevented by NAC therapy. SHR had lower renal DDAH activity than WKY, whereas NAC-treated animals did not. Renal superoxide production was higher in SHR than in WKY, whereas NAC therapy prevented it. NAC therapy was also associated with higher GSH-to-oxidized GSH ratio in SHR kidneys. Moreover, NAC reduced oxidative stress damage in SHR. The observed antihypertensive effects of NAC in young SHR might be due to restoration of DDAH activity to reduce ADMA, leading to attenuation of oxidative stress. Our findings highlight the impact of NAC on the development of hypertension by regulating ADMA-DDAH pathway.

Activity/inactivity circadian rhythm shows high similarities between young obesity-induced rats and old rats.

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Bravo Santos, R; Delgado, J; Cubero, J; Franco, L; Ruiz-Moyano, S; Mesa, M; Rodríguez, A B; Uguz, C; Barriga, C

2016-03-01

The objective of the present study was to compare differences between elderly rats and young obesity-induced rats in their activity/inactivity circadian rhythm. The investigation was motivated by the differences reported previously for the circadian rhythms of both obese and elderly humans (and other animals), and those of healthy, young or mature individuals. Three groups of rats were formed: a young control group which was fed a standard chow for rodents; a young obesity-induced group which was fed a high-fat diet for four months; and an elderly control group with rats aged 2.5 years that was fed a standard chow for rodents. Activity/inactivity data were registered through actimetry using infrared actimeter systems in each cage to detect activity. Data were logged on a computer and chronobiological analysis were performed. The results showed diurnal activity (sleep time), nocturnal activity (awake time), amplitude, acrophase, and interdaily stability to be similar between the young obesity-induced group and the elderly control group, but different in the young control group. We have concluded that obesity leads to a chronodisruption status in the body similar to the circadian rhythm degradation observed in the elderly.

Some pharmacological effects of cinnamon and ginger herbs in obese diabetic rats

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Shalaby, Mostafa Abbas; Saifan, Hamed Yahya

2014-01-01

Aims: The present study was designed to assess some pharmacological effects of cinnamon (CAE) and ginger (GAE) aqueous extracts in obese diabetic rats, and to elucidate the potential mechanisms. Materials and Methods: Forty-two Sprague-Dawley rats were randomized into 6 equal groups. Group 1 was a negative control and the other groups were rendered obese by feeding rats on high-fat diet for 4 weeks. The obese rats were subcutaneously injected with alloxan for 5*days to induce diabetes. Group ...

Some pharmacological effects of cinnamon and ginger herbs in obese diabetic rats

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Shalaby, Mostafa Abbas; Saifan, Hamed Yahya

2014-01-01

Aims: The present study was designed to assess some pharmacological effects of cinnamon (CAE) and ginger (GAE) aqueous extracts in obese diabetic rats, and to elucidate the potential mechanisms. Materials and Methods: Forty-two Sprague-Dawley rats were randomized into 6 equal groups. Group 1 was a negative control and the other groups were rendered obese by feeding rats on high-fat diet for 4 weeks. The obese rats were subcutaneously injected with alloxan for 5*days to induce diabetes. Group 2 was a positive control, and Groups 3, 4, 5 and 6 were orally given CAE in doses 200 and 400 mg/kg and GAE in the same doses, respectively for 6 weeks. Blood samples were collected for serum biochemical analyses. Kidneys were dissected out to assay activity of tissue antioxidant enzymes: Superoxide dismutase, glutathione peroxidase and catalase. Results: CAE and GAE significantly reduced body weight and body fat mass; normalized serum levels of liver enzymes; improved lipid profile; decreased blood glucose and leptin and increased insulin serum levels in obese diabetic rats. Both extracts also increased activity of kidney antioxidant enzymes. Conclusion: CAE and GAE exhibit anti-obesity, hepatoprotective, hypolipidemic, antidiabetic and anti-oxidant effects in obese diabetic rats. These results confirm the previous reports on both extracts. The potential mechanisms underlying these effects are fully discussed and clarified. Our results affirm the traditional use of cinnamon and ginger for treating patients suffering from obesity and diabetes. The obese diabetic rat model used in this study is a novel animal model used in pharmacology researches. PMID:26401364

Leucine and protein metabolism in obese Zucker rats.

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Pengxiang She

Full Text Available Branched-chain amino acids (BCAAs are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1-(14C]-leucine metabolism, tissue-specific protein synthesis and branched-chain keto-acid (BCKA dehydrogenase complex (BCKDC activities. Male obese Zucker rats (11-weeks old had increased body weight (BW, 53%, liver (107% and fat (∼300%, but lower plantaris and gastrocnemius masses (-21-24%. Plasma BCAAs and BCKAs were elevated 45-69% and ∼100%, respectively, in obese rats. Processes facilitating these rises appeared to include increased dietary intake (23%, leucine (Leu turnover and proteolysis [35% per g fat free mass (FFM, urinary markers of proteolysis: 3-methylhistidine (183% and 4-hydroxyproline (766%] and decreased BCKDC per g kidney, heart, gastrocnemius and liver (-47-66%. A process disposing of circulating BCAAs, protein synthesis, was increased 23-29% by obesity in whole-body (FFM corrected, gastrocnemius and liver. Despite the observed decreases in BCKDC activities per gm tissue, rates of whole-body Leu oxidation in obese rats were 22% and 59% higher normalized to BW and FFM, respectively. Consistently, urinary concentrations of eight BCAA catabolism-derived acylcarnitines were also elevated. The unexpected increase in BCAA oxidation may be due to a substrate effect in liver. Supporting this idea, BCKAs were elevated more in liver (193-418% than plasma or muscle, and per g losses of hepatic BCKDC activities were completely offset by increased liver mass, in contrast to other tissues. In summary, our results indicate that plasma BCKAs may represent a more sensitive metabolic signature for obesity than BCAAs. Processes supporting elevated BCAA]BCKAs in the obese Zucker rat include increased dietary intake, Leu and protein

The effects of running exercise on oxidative capacity and PGC-1α mRNA levels in the soleus muscle of rats with metabolic syndrome.

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Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Kouzaki, Motoki; Gu, Ning; Takeda, Isao; Tsuda, Kinsuke; Ishihara, Akihiko

2012-03-01

Skeletal muscles in animals with metabolic syndrome exhibit reduced oxidative capacity. We investigated the effects of running exercise on fiber characteristics, oxidative capacity, and mRNA levels in the soleus muscles of rats with metabolic syndrome [SHR/NDmcr-cp (cp/cp); CP]. We divided 5-week-old CP rats into non-exercise (CP) and exercise (CP-Ex) groups. Wistar-Kyoto rats (WKY) were used as the control group. CP-Ex rats were permitted voluntary exercise on running wheels for 10 weeks. Triglyceride levels were higher and adiponectin levels lower in the CP and CP-Ex groups than in the WKY group. However, triglyceride levels were lower and adiponectin levels higher in the CP-Ex group than in the CP group. The soleus muscles in CP-Ex rats contained only high-oxidative type I fibers, whereas those in WKY and CP rats contained type I, IIA, and IIC fibers. Muscle succinate dehydrogenase (SDH) activity was higher in the CP-Ex group than in the CP group; there was no difference in SDH activity between the WKY and CP-Ex groups. Muscle proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA levels were higher in the CP-Ex group than in the CP group; there was no difference in PGC-1α mRNA levels between the WKY and CP-Ex groups. In CP-Ex rats, longer running distance was associated with increased muscle SDH activity and PGC-1α mRNA levels. We concluded that running exercise restored decreased muscle oxidative capacity and PGC-1α mRNA levels and improved hypertriglyceridemia in rats with metabolic syndrome.

Effects of Obesity on Bone Mass and Quality in Ovariectomized Female Zucker Rats

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Rafaela G. Feresin

2014-01-01

Full Text Available Obesity and osteoporosis are two chronic conditions that have been increasing in prevalence. Despite prior data supporting the positive relationship between body weight and bone mineral density (BMD, recent findings show excess body weight to be detrimental to bone mass, strength, and quality. To evaluate whether obesity would further exacerbate the effects of ovariectomy on bone, we examined the tibiae and fourth lumbar (L4 vertebrae from leptin receptor-deficient female (Leprfa/fa Zucker rats and their heterozygous lean controls (Leprfa/+ that were either sham-operated or ovariectomized (Ovx. BMD of L4 vertebra was measured using dual-energy X-ray absorptiometry, and microcomputed tomography was used to assess the microstructural properties of the tibiae. Ovariectomy significantly (P<0.001 decreased the BMD of L4 vertebrae in lean and obese Zucker rats. Lower trabecular number and greater trabecular separation (P<0.001 were also observed in the tibiae of lean- and obese-Ovx rats when compared to sham rats. However, only the obese-Ovx rats had lower trabecular thickness (Tb.Th (P<0.005 than the other groups. These findings demonstrated that ovarian hormone deficiency adversely affected bone mass and quality in lean and obese rats while obesity only affected Tb.Th in Ovx-female Zucker rats.

WNIN/GR-Ob - an insulin-resistant obese rat model from inbred WNIN strain.

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Harishankar, N; Vajreswari, A; Giridharan, N V

2011-09-01

WNIN/GR-Ob is a mutant obese rat strain with impaired glucose tolerance (IGT) developed at the National Institute of Nutrition (NIN), Hyderabad, India, from the existing 80 year old Wistar rat (WNIN) stock colony. The data presented here pertain to its obese nature along with IGT trait as evidenced by physical, physiological and biochemical parameters. The study also explains its existence, in three phenotypes: homozygous lean (+/+), heterozygous carrier (+/-) and homozygous obese (-/-). Thirty animals (15 males and 15 females) from each phenotype (+/+, +/-, -/-) and 24 lean and obese (6 males and 6 females) rats were taken for growth and food intake studies respectively. Twelve adult rats from each phenotype were taken for body composition measurement by total body electrical conductivity (TOBEC); 12 rats of both genders from each phenotype at different ages were taken for clinical chemistry parameters. Physiological indices of insulin resistance were calculated according to the homeostasis model assessment for insulin resistance (HOMA-IR) and also by studying U¹⁴C 2-deoxy glucose uptake (2DG). WNINGR-Ob mutants had high growth, hyperphagia, polydipsia, polyurea, glycosuria, and significantly lower lean body mass, higher fat mass as compared with carrier and lean rats. These mutants, at 50 days of age displayed abnormal response to glucose load (IGT), hyperinsulinaemia, hypertriglyceridaemia, hypercholesterolaemia and hyperleptinaemia. Basal and insulin-stimulated glucose uptakes by diaphragm were significantly decreased in obese rats as compared with lean rats. Obese rats of the designated WNIN/GR-Ob strain showed obesity with IGT, as adjudged by physical, physiological and biochemical indices. These indices varied among the three phenotypes, being lowest in lean, highest in obese and intermediate in carrier phenotypes thereby suggesting that obesity is inherited as autosomal incomplete dominant trait in this strain. This mutant obese rat model is easy to

Intestinal ion transport in rats with spontaneous arterial hypertension.

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Lübcke, R; Barbezat, G O

1988-08-01

1. Ion balance, intestinal ion transport in vivo with luminal Ringer, and direct voltage clamping in vivo with luminal Ringer and sodium-free choline-Ringer were studied in young (40 days old) and adult (120 days old) spontaneously hypertensive rats (SHR) and age-matched normotensive controls (Wistar-Kyoto rats, WKY). 2. Faecal sodium output was significantly higher in SHR compared with WKY in both young (+67%) and adult (+43%) rats. 3. Small-intestinal sodium absorption was equal in young SHR and WKY, but significantly greater net sodium absorption was found in the ileum of adult SHR. In contrast, net sodium absorption was reduced from the colon of both young and adult SHR. 4. In adult SHR, the colonic transepithelial short-circuit current (Isc) and the transepithelial potential difference (PD) were significantly higher, whereas the transepithelial membrane resistance (Rm) was significantly lower than in WKY. There was an identical drop in Isc in both strains when luminal sodium was replaced by choline. These data cannot be explained by increased electrogenic cation (sodium) absorption in the SHR, but would favour chloride secretion. 5. It is suggested that in SHR membrane electrolyte transport abnormalities may also be present in the epithelial cells of the small and large intestine, as have been demonstrated already in blood cells by several investigators. The SHR may become an interesting experimental animal model for the study of generalized ion transport disorders.

Serum Fetuin-A Levels Related with Microalbuminuria in Diet-Induced Obese Rats

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Yanyan Li

2013-01-01

Full Text Available The aim of the study was to investigate the association between elevated serum fetuin-A and increased urine albumin excretion in obese rats, and whether increased urine albumin excretion was modified by improving hepatic steatosis and lipid metabolism disorder. Male Wistar rats 4 weeks in age were randomly divided into three groups and fed with normal chow (control group, high-fat chow (obesity group, or high-fat chow plus fenofibrate (fenofibrate group. After 24 weeks, both body weight and visceral fat/body weight ratio in obese rats were higher than in controls. A difference in serology markers and pathology associated with hepatic steatosis was also found among the three groups. Serum fetuin-A and the expression of NF-κB in the liver were increased, while serum adiponectin was decreased in obese rats in comparison to controls (. Urinary albumin/creatinine ratio (ACR was increased in the obesity group compared to controls (. The fenofibrate intervention reduced serum fetuin-A and NF-κB expression in the liver and increased serum adiponectin compared to obese rats and was accompanied by decrease in ACR. A positive correlation was found between ACR and fetuin-A (, , and a negative correlation was found between ACR and adiponectin (, . We conclude that elevated fetuin-A levels are associated with microalbuminuria in obese rats, and abnormal albuminuria is reversible by improving hepatic steatosis.

Carbenoxolone treatment ameliorated metabolic syndrome in WNIN/Ob obese rats, but induced severe fat loss and glucose intolerance in lean rats.

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Siva Sankara Vara Prasad Sakamuri

Full Text Available BACKGROUND: 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1 regulates local glucocorticoid action in tissues by catalysing conversion of inactive glucocorticoids to active glucocorticoids. 11β-HSD1 inhibition ameliorates obesity and associated co-morbidities. Here, we tested the effect of 11β-HSD inhibitor, carbenoxolone (CBX on obesity and associated comorbidities in obese rats of WNIN/Ob strain, a new animal model for genetic obesity. METHODOLOGY/PRINCIPAL FINDINGS: Subcutaneous injection of CBX (50 mg/kg body weight or volume-matched vehicle was given once daily for four weeks to three month-old WNIN/Ob lean and obese rats (n = 6 for each phenotype and for each treatment. Body composition, plasma lipids and hormones were assayed. Hepatic steatosis, adipose tissue morphology, inflammation and fibrosis were also studied. Insulin resistance and glucose intolerance were determined along with tissue glycogen content. Gene expressions were determined in liver and adipose tissue. CBX significantly inhibited 11β-HSD1 activity in liver and adipose tissue of WNIN/Ob lean and obese rats. CBX significantly decreased body fat percentage, hypertriglyceridemia, hypercholesterolemia, insulin resistance in obese rats. CBX ameliorated hepatic steatosis, adipocyte hypertrophy, adipose tissue inflammation and fibrosis in obese rats. Tissue glycogen content was significantly decreased by CBX in liver and adipose tissue of obese rats. Severe fat loss and glucose- intolerance were observed in lean rats after CBX treatment. CONCLUSIONS/SIGNIFICANCE: We conclude that 11β-HSD1 inhibition by CBX decreases obesity and associated co-morbidities in WNIN/Ob obese rats. Our study supports the hypothesis that inhibition of 11β-HSD1 is a key strategy to treat metabolic syndrome. Severe fat loss and glucose -intolerance by CBX treatment in lean rats suggest that chronic 11β-HSD1 inhibition may lead to insulin resistance in normal conditions.

In vitro demonstration of anti-lipogenic activity in serum from obese rats

International Nuclear Information System (INIS)

Harris, R.B.S.; Martin, R.J.

1986-01-01

Studies with parabiosed rats provide evidence for a humoral factor, originating in obese animals, that specifically inhibits adipose lipogenesis. A bioassay was developed that allows serum from obese rats to be tested for this factor in vitro. Adipocytes are isolated from epididymal fat of 250g Sprague-Dawley rats. The cells are preincubated at 37 0 C for 1 or 12 hrs, in TC199 media containing 1.1 mg/ml glucose, 0.1 M Hepes and 2% serum. Following preincubation, the cells are washed 3 times and resuspended in serum-free media. Aliquots of cells are tested for metabolic activity in a subsequent 2 hour radiolabelled incubation in serum-free media with the addition of 0.5 μCi/ml U- 14 C-glucose. Basal, insulin (100 μU/ml) and norepinephrine (0.1 μg/ml) stimulated rates of glucose oxidation and conversion to triglyceride fatty acids are measured. Using serum from ad libitum fed rats as control, preincubation with serum from obese rats (20 days at 2 x normal intake) depressed basal and insulin stimulated glucose oxidation, and basal fatty acid synthesis. Serum from obese parabiotic rats and parabiotic partners of obese rats depressed basal fatty acid synthesis. This assay allows us to test serum for anti-lipogenic activity and may be used to identify the factor responsible for this activity in obese animals

Decrease of Perivascular Adipose Tissue Browning Is Associated With Vascular Dysfunction in Spontaneous Hypertensive Rats During Aging

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Ling-Ran Kong

2018-04-01

Full Text Available Functional perivascular adipose tissue (PVAT is necessary to maintain vascular physiology through both mechanical support and endocrine or paracrine ways. PVAT shows a brown adipose tissue (BAT-like feature and the browning level of PVAT is dependent on the anatomic location and species. However, it is not clear whether PVAT browning is involved in the vascular tone regulation in spontaneously hypertensive rats (SHRs. In the present study, we aimed to illustrate the effect of aging on PVAT browning and subsequent vasomotor reaction in SHRs. Herein we utilized histological staining and western blot to detect the characteristics of thoracic PVAT (tPVAT in 8-week-old and 16-week-old SHR and Wistar-Kyoto (WKY rats. We also detected vascular reactivity analysis to determine the effect of tPVAT on vasomotor reaction during aging. The results showed that tPVAT had a similar phenotype to BAT, including smaller adipocyte size and positive uncoupling protein-1 (UCP1 staining. Interestingly, the tPVAT of 8-week-old SHR showed increased BAT phenotypic marker expression compared to WKY, whereas the browning level of tPVAT had a more dramatic decrease from 8 to 16 weeks of age in SHR than age-matched WKY rats. The vasodilation effect of tPVAT on aortas had no significant difference in 8-week-old WKY and SHR, whereas this effect is obviously decreased in 16-week-old SHR compared to WKY. In contrast, tPVAT showed a similar vasoconstriction effect in 8- or 16-week-old WKY and SHR rats. Moreover, we identified an important vasodilator adenosine, which regulates adipocyte browning and may be a potential PVAT-derived relaxing factor. Adenosine is dramatically decreased from 8 to 16 weeks of age in the tPVAT of SHR. In summary, aging is associated with a decrease of tPVAT browning and adenosine production in SHR rats. These may result in attenuated vasodilation effect of the tPVAT in SHR during aging.

Arginase promotes endothelial dysfunction and hypertension in obese rats.

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Johnson, Fruzsina K; Peyton, Kelly J; Liu, Xiao-Ming; Azam, Mohammed A; Shebib, Ahmad R; Johnson, Robert A; Durante, William

2015-02-01

This study investigated whether arginase contributes to endothelial dysfunction and hypertension in obese rats. Endothelial function and arginase expression were examined in skeletal muscle arterioles from lean and obese Zucker rats (ZRs). Arginase activity, arginine bioavailability, and blood pressure were measured in lean and obese animals. Arginase activity and expression was increased while global arginine bioavailability decreased in obese ZRs. Acetylcholine or luminal flow caused dilation of isolated skeletal muscle arterioles, but this was reduced or absent in vessels from obese ZRs. Treatment of arterioles with a nitric oxide synthase inhibitor blocked dilation in lean arterioles and eliminated differences among lean and obese vessels. In contrast, arginase inhibitors or l-arginine enhanced vasodilation in obese ZRs and abolished differences between lean and obese animals, while d-arginine had no effect. Finally, mean arterial blood pressure was significantly increased in obese ZRs. However, administration of l-arginine or arginase inhibitors lowered blood pressure in obese but not lean animals, and this was associated with an improvement in systemic arginine bioavailability. Arginase promotes endothelial dysfunction and hypertension in obesity by reducing arginine bioavailability. Therapeutic approaches targeting arginase represent a promising approach in treating obesity-related vascular disease. © 2014 The Obesity Society.

Exercise training prevents the attenuation of anesthetic pre-conditioning-mediated cardioprotection in diet-induced obese rats.

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Li, L; Meng, F; Li, N; Zhang, L; Wang, J; Wang, H; Li, D; Zhang, X; Dong, P; Chen, Y

2015-01-01

Obesity abolishes anesthetic pre-conditioning-induced cardioprotection due to impaired reactive oxygen species (ROS)-mediated adenosine monophosphate-activated protein kinase (AMPK) pathway, a consequence of increased basal myocardial oxidative stress. Exercise training has been shown to attenuate obesity-related oxidative stress. This study tests whether exercise training could normalize ROS-mediated AMPK pathway and prevent the attenuation of anesthetic pre-conditioning-induced cardioprotection in obesity. Male Sprague-Dawley rats were divided into lean rats fed with control diet and obese rats fed with high-fat diet. After 4 weeks of feeding, lean and obese rats were assigned to sedentary conditions or treadmill exercise for 8 weeks. There was no difference in infarct size between lean sedentary and obese sedentary rats after 25 min of myocardial ischemia followed by 120 min reperfusion. In lean rats, sevoflurane equally reduced infarct size in lean sedentary and lean exercise-trained rats. Molecular studies revealed that AMPK activity, endothelial nitric oxide synthase, and superoxide production measured at the end of ischemia in lean rats were increased in response to sevoflurane. In obese rats, sevoflurane increased the above molecular parameters and reduced infarct size in obese exercise-trained rats but not in obese sedentary rats. Additional study showed that obese exercise-trained rats had decreased basal oxidative stress than obese sedentary rats. The results indicate that exercise training can prevent the attenuation of anesthetic cardioprotection in obesity. Preventing the attenuation of this strategy may be associated with reduced basal oxidative stress and normalized ROS-mediated AMPK pathway, but the causal relationship remains to be determined. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Swimming intervention mitigates HFD-induced obesity of rats through PGC-1α-irisin pathway.

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Yang, X-Q; Yuan, H; Li, J; Fan, J-J; Jia, S-H; Kou, X-J; Chen, N

2016-05-01

Irisin, a newly discovered myokine, can drive the browning of white adipocytes to control body weight or mitigate obesity progression through regulating energy metabolism. However, the underlying mechanisms or specific signal pathways of exercise-induced irisin on the management of obesity are still unclear. Totally 30 rats were subjected to high fat diet (HFD) feeding for 8 weeks to establish the rat model with obesity successfully. HFD-induced obese model rats were provided with 8 weeks swimming intervention at moderate intensity for exploring the treatment of obesity through exercise intervention. In addition, another 15 rats were subjected to HFD feeding coupled with total 16 weeks swimming intervention at a moderate intensity from the beginning of the experiment, which was used for exploring the prevention of obesity through exercise intervention. Blood and gastrocnemius samples were harvested from obese rats after swimming intervention to explore its specific signal pathways through ELISA analysis and Western blotting. HFD feeding of rats for 8 weeks could lead to the obesity due to the disorders of lipid metabolism. Totally 8 weeks swimming intervention at moderate intensity for rats with obesity could obviously alleviate the progression of obesity and 16 weeks swimming intervention from the beginning of the experiment could significantly inhibit the development of obesity. Meanwhile, swimming intervention could result in an increased phosphorylation of AMPK and up-regulation of irisin and PGC-1α as the biomarkers of energy metabolism. Exercise intervention can activate PGC-1α-dependent irisin to induce the browning of white adipocytes, thus inhibiting or alleviating the occurrence and development of obesity.

Cold-increase in brown fat thyroxine 5'-monodeiodinase is attenuated in Zucker obese rat

International Nuclear Information System (INIS)

Wu, S.Y.; Stern, J.S.; Fisher, D.A.; Glick, Z.

1987-01-01

In this study the authors examined the possibility that the reduced brown adipose tissue (BAT) thermogenesis in the Zucker obese rat may result from a limited capacity for enzymic conversion of thyroxine (T 4 ) to triiodothyronine (T 3 ) in BAT. A total of 34 lean and obese rats, ∼4 mo old were divided into three treatment groups: group 1 (5 lean and 6 obese) was fed Purina rat chow for 21 days, and group two (5 lean and 6 obese) was fed a cafeteria diet for 21 days, and groups 3 (6 lean and 6 obese) was fed Purina rat chow and maintained in the cold (8 +/- 1 0 C) for 7 days. Activity of T 4 5'-deiodinase was determined as the rate of T 3 production from added T 4 under controlled in vitro conditions. Serum T 4 and T 3 were determined by radioimmunoassay. The rate of T 4 -to-T 3 conversion in BAT was similar in the lean and obese rats maintained at room temperature, whether fed rat chow or a cafeteria diet. However, expressed per scapular BAT depot, lean rats exposed to cold displayed about a fivefold increase in BAT T 3 production whereas only a small increase was observed in the cold-exposed obese rats. Serum T 3 levels tended to be reduced in the Zucker obese rats. The data indicate a reduced capacity for T 3 production of Zucker rat BAT exposed to cold. This defect may account for the reduced tolerance of the obese animals to cold, but it does not account for their reduced diet-induced BAT thermogenesis

Metabolic adjustments with the development, treatment, and recurrence of obesity in obesity-prone rats.

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MacLean, Paul S; Higgins, Janine A; Johnson, Ginger C; Fleming-Elder, Brooke K; Peters, John C; Hill, James O

2004-08-01

Obesity is reaching epidemic proportions and predisposes afflicted individuals to several comorbidities. For these individuals, losing weight has proven to be an easier feat than maintaining a reduced weight. In obesity-prone rats, we examined if there is a metabolic propensity to regain weight after a period of significant weight loss. Twenty-four-hour energy expenditure (EE), sleeping metabolic rate (SMR), and nonprotein respiratory quotient (NPRQ) were obtained by indirect calorimetry with urinary nitrogen analysis and normalized to fat mass (FM) and fat-free mass (FFM) acquired by dual-energy X-ray absorptiometry. Obesity-prone rats were examined after free access to a high-fat diet for 16 wk to establish the obese state. They were again examined after 2 wk of calorie restriction, which reduced body weight (14%) and FM (32%). Rats were again examined after a further 8 wk of intake-regulated weight maintenance or ad libitum feeding that led to weight regain. Metabolic data were compared with preobese and age-matched controls. Weight loss suppressed EE and SMR beyond what was expected for the change in metabolic mass. This elevated metabolic efficiency persisted throughout weight maintenance but resolved after 8 wk of regain. Adjusted NPRQ values were elevated in weight-maintained and weight-regaining rats, suggesting a preference for carbohydrate utilization. These data support the concept that weight reduction in obesity is accompanied by metabolic adjustments beyond the drive to consume calories that predispose to weight regain, and some aspects of this adjustment persist with prolonged weight maintenance and during weight regain.

Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

Energy Technology Data Exchange (ETDEWEB)

Rahmani, N.H.; Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

1991-01-01

The binding of {sup 3}H-naltrexone, an opiate receptor antagonist, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. {sup 3}H-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of {sup 3}H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B{sub max}value) and apparent dissociation constant (K{sub d} value) values of {sup 3}H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midgrain, cortex and spinal cord of WKY and SHR rates did not differ. The B{sub max} value of {sup 3}H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K{sub d} values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with {sup 3}H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats.

Dissociation of changes in the permeability of the blood-brain barrier from catecholamine-induced changes in blood pressure of normotensive and spontaneously hypertensive rats

International Nuclear Information System (INIS)

Sankar, R.; Domer, F.R.; Taylor, B.

1982-01-01

Researchers have studied the effects of the pressor catecholamine, dopamine, and the depressor catecholamine, isoproterenol, on the systemic blood pressure and the permeability of the blood-brain barrier (BBB) to albumin in normotensive (WKY) and spontaneously hypertensive (SHR) rats. The rats were anesthetized with pentobarbital. The permeability of the BBB to protein was measured by the extravasation of radioiodinated serum albumin (RISA). The permeability was decreased by both catecholamines despite the dose-dependent, yet opposite, changes in blood pressure in the WKY rats. The blood pressure response to both of the catecholamines was enhanced in the SHR rats. Isoproterenol caused a decrease in the permeability of the BBB in the SHR but dopamine did not. Results with both WKY and SHR rats are suggestive of an adrenergically-mediated decrease in movement across the BBB of compounds of large molecular weight, regardless of changes in blood pressure

Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats

International Nuclear Information System (INIS)

Hashimoto, K.; Hattori, T.; Murakami, K.; Suemaru, S.; Kawada, Y.; Kageyama, J.; Ota, Z.

1985-01-01

The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of 125 I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neurointermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR

Daily Rhythms of Feeding in the Genetically Obese and Lean Zucker Rats

NARCIS (Netherlands)

Alingh Prins, Ab; Jong-Nagelsmit, Annemarie de; Keijser, Jan; Strubbe, Jan H.

1986-01-01

Feeding patterns were examined in obese (fa/fa) and lean (Fa/-) adult Zucker rats over the light-dark cycle during 14 days. Obese rats eat more than lean rats especially during the dark phase. Light and dark feeding expressed as percentage of 24 hr intake showed no significant differences between

Hepatic expression of spermatogenic genes and their transiently remarkable downregulations in Wistar-Kyoto rats in response to lead-nitrate administration: strain-difference in the gene expression patterns.

Science.gov (United States)

Nemoto, Kiyomitsu; Ito, Sei; Yoshida, Chiaki; Miyata, Misaki; Kojima, Misaki; Degawa, Masakuni

2011-06-01

Administration of lead ion (Pb) to rats and mice affects hepatic functions such as the induction of hepatic cell proliferation and upregulation of cholesterol biosynthesis. To identify the genes for which expression changes in response to Pb-administration, we analyzed hepatic gene expression patterns in stroke-prone spontaneously hypertensive rat (SHRSP), its normotensive control, Wistar-Kyoto rat (WKY), and Spraque-Dawley (SD) rat strains, 3, 6, and 12 hr later after single i.v. injection of lead nitrate (LN) at a dose of 100 µmol using a DNA microarray technique. The data analysis demonstrated that the expression of a great number of genes was transiently and remarkably downregulated 3 hr after LN-injection, and then recovered to control levels only in LN-injected WKY. These normal hepatic expression levels in WKY and SHRSP were much higher than those in SD rats. Furthermore, most of these genes were ones thought to be expressed specifically in the spermatids and/or testes; i.e. genes encoding protamin 1, transition protein 1, and transition protein 2. These findings suggest that the regulation system common to expression of all of these genes could be a target site of Pb-toxic action, at least, in the liver of WKY, and that this system might be similar to the system essential for spermatogenesis, especially spermiogenesis, in the testis. In addition, it appears that clarifying the cause of the difference between the systems of WKY and SHRSP might aid in identifying the pathologic genes in SHRSP. Finally, it will be an important to clarify how the products of the genes related to spermatogenesis, including spermiogenesis, are functional in the livers of WKY and SHRSP.

Grooming behavior of spontaneously hypertensive rats

NARCIS (Netherlands)

Buuse, M. van den; Jong, Wybren de

1987-01-01

In an open field spontaneously hypertensive rats (SHR) exhibited lower scores for grooming when compared to their normotensive controls, the Wistar Kyoto rats (WKY). After i.c.v. injection of 1 μg ACTH1–24 cumulative 50-min grooming scores were lower in SHR. Analysis of subscores indicated that the

Vliv chronického podávání captoprilu na vasokonstrikci vyvolanou noradrenalinem (NA) u SHR a WKY : In vivo studie

Czech Academy of Sciences Publication Activity Database

Pintérová, Mária; Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

2008-01-01

Roč. 50, č. 9 (2008), K168-K168 ISSN 0010-8650. [Konference ČSH /25./, Konference prac. skupiny preventivní kardiologie ČKS /17./, Konference prac. skupiny srdeční selhání ČKS /13./. 02.10.2008-04.10.2008, Český Krumlov] R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/08/0139 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * captopril * norepinephrine-induced vasoconstriction * SHR and WKY rat Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

Nicotine improves obesity and hepatic steatosis and ER stress in diet-induced obese male rats.

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Seoane-Collazo, Patricia; Martínez de Morentin, Pablo B; Fernø, Johan; Diéguez, Carlos; Nogueiras, Rubén; López, Miguel

2014-05-01

Nicotine, the main addictive component of tobacco, promotes body weight reduction in humans and rodents. Recent evidence has suggested that nicotine acts in the central nervous system to modulate energy balance. Specifically, nicotine modulates hypothalamic AMP-activated protein kinase to decrease feeding and to increase brown adipose tissue thermogenesis through the sympathetic nervous system, leading to weight loss. Of note, most of this evidence has been obtained in animal models fed with normal diet or low-fat diet (LFD). However, its effectiveness in obese models remains elusive. Because obesity causes resistance towards many factors involved in energy homeostasis, the aim of this study has been to compare the effect of nicotine in a diet-induced obese (DIO) model, namely rats fed a high-fat diet, with rats fed a LFD. Our data show that chronic peripheral nicotine treatment reduced body weight by decreasing food intake and increasing brown adipose tissue thermogenesis in both LFD and DIO rats. This overall negative energy balance was associated to decreased activation of hypothalamic AMP-activated protein kinase in both models. Furthermore, nicotine improved serum lipid profile, decreased insulin serum levels, as well as reduced steatosis, inflammation, and endoplasmic reticulum stress in the liver of DIO rats but not in LFD rats. Overall, this evidence suggests that nicotine diminishes body weight and improves metabolic disorders linked to DIO and might offer a clear-cut strategy to develop new therapeutic approaches against obesity and its metabolic complications.

Pre-existing differences and diet-induced alterations in striatal dopamine systems of obesity-prone rats.

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Vollbrecht, Peter J; Mabrouk, Omar S; Nelson, Andrew D; Kennedy, Robert T; Ferrario, Carrie R

2016-03-01

Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2 /D3 dopamine receptor-mediated transmission prior to and after consumption of "junk-foods" in obesity-prone and obesity-resistant rats. Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2 /D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. © 2016 The Obesity Society.

Long-Term Low Intensity Physical Exercise Attenuates Heart Failure Development in Aging Spontaneously Hypertensive Rats

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Luana U. Pagan

2015-04-01

Full Text Available Background: Physical exercise is a strategy to control hypertension and attenuate pressure overload-induced cardiac remodeling. The influence of exercise on cardiac remodeling during uncontrolled hypertension is not established. We evaluated the effects of a long-term low intensity aerobic exercise protocol on heart failure (HF development and cardiac remodeling in aging spontaneously hypertensive rats (SHR. Methods: Sixteen month old SHR (n=50 and normotensive Wistar-Kyoto (WKY, n=35 rats were divided into sedentary (SED and exercised (EX groups. Rats exercised in treadmill at 12 m/min, 30 min/day, 5 days/week, for four months. The frequency of HF features was evaluated at euthanasia. Statistical analyses: ANOVA and Tukey or Mann-Whitney, and Goodman test. Results: Despite slightly higher systolic blood pressure, SHR-EX had better functional capacity and lower HF frequency than SHR-SED. Echocardiography and tissue Doppler imaging showed no differences between SHR groups. In SHR-EX, however, left ventricular (LV systolic diameter, larger in SHR-SED than WKY-SED, and endocardial fractional shortening, lower in SHR-SED than WKY-SED, had values between those in WKY-EX and SHR-SED not differing from either group. Myocardial function, assessed in LV papillary muscles, showed improvement in SHR-EX over SHR-SED and WKY-EX. LV myocardial collagen fraction and type I and III collagen gene expression were increased in SHR groups. Myocardial hydroxyproline concentration was lower in SHR-EX than SHR-SED. Lysyl oxidase gene expression was higher in SHR-SED than WKY-SED. Conclusion: Exercise improves functional capacity and reduces decompensated HF in aging SHR independent of elevated arterial pressure. Improvement in functional status is combined with attenuation of LV and myocardial dysfunction and fibrosis.

New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein

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Ana Isabel Garcia Diaz

2016-04-01

Full Text Available The Wistar Kyoto (WKY rat and the spontaneously hypertensive (SHR rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN and metabolic syndrome, respectively. Novel transgenic (Tg strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP under the rat elongation factor 1 alpha (EF1a promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminary in vitro and in vivo imaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades.

Satiety in the obese Zucker rat: effects of carbohydrate type and acarbose (Bay g 5421).

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Maggio, C A; Vasselli, J R

1989-09-01

Despite the obese Zucker rat's hyperphagia on carbohydrate diets such as laboratory chow, this laboratory has found that its satiety response to glucose and other simple sugars is comparable to that of its lean control rat. To further investigate carbohydrate satiety in the Zucker rat, the short-term feeding behavior of obese and lean rats was observed following intragastric infusions (7.2 kcal in 10 ml) of corn starch and the starch hydrolysates Polycose and dextrin. There were no reliable between-genotype differences in the feeding inhibitory effects of Polycose and dextrin. However, in obese rats, the satiety effect of corn starch was delayed and reduced compared to that observed in lean rats (p less than 0.04). To modify the effect of corn starch, rats were administered 0.2 or 0.6 mg/infusion of the carbohydrate digestive inhibitor acarbose (Bay g 5421). Acarbose significantly reduced the satiety effect of corn starch in lean rats (p less than 0.001), and further attenuated satiety in obese rats (p less than 0.02). Since secretion of pancreatic amylase, the enzyme that initiates starch digestion, is decreased in obese rats, this result suggests that alterations of digestive and/or absorptive processes may underlie the obese rat's impaired satiety response to complex carbohydrate.

EFFECTS OF RESVERATROL ON LIVER FUNCTION OF OBESE FEMALE WISTAR RATS

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Nádia Araújo Miguel

2016-07-01

Full Text Available Resveratrol has antioxidant, anti-inflammatory, lipolytic, and antifibrotic properties, which may be useful in supplementation of obese patients and with liver problems. This study evaluated the effects of 6-week resveratrol supplementation on the lipid profile and liver function of female Wistar rats fed a high-fat diet to induce obesity. Sixty-four Wistar rats were divided into 4 groups (n = 16: the control group (C; the control obese group (CO; the resveratrol group (R; and the resveratrol obese group (RO. At the end of the experiment, the animals were anesthetized for blood collection and subsequent euthanasia for collection of liver biopsy. The parameters for body weight, liver weight, retroperitoneal fat weight, serum lipid and liver profiles and histopathological analysis were evaluated. The 6-week resveratrol administration did not induce weight loss nor did it reduce the lipid profile; however, it decreased the liver enzymes aspartate aminotransferase (AST and alkaline phosphatase (ALP and reduced the incidence of steatosis (75.0% in group RO compared with group CO (81.2%. Thus, we concluded that resveratrol supplementation for the short period of six weeks had a beneficial effect on liver function by reducing hepatic steatosis and the liver enzymes AST and ALP in obese female rats. Keywords: liver function; obesity; rats; resveratrol.

Weight Loss and Melatonin Reduce Obesity-Induced Oxidative Damage in Rat Testis

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Dogan Atilgan

2013-01-01

Full Text Available Aim. We aimed to evaluate the antioxidant effects of weight loss and melatonin on the obesity-induced oxidative damage in rat testes. Materials and Methods. 28 male Wistar albino rats were randomly divided into 4 groups, each consisting of 7 rats: control group (Group 1, obesity group (Group 2, obesity + MLT group (Group 3, and weight loss group (Group 4. Rats were weighed at the beginning and at the end of the study. Bilateral orchiectomy was performed and 5 cc blood samples were obtained from all of the rats. Superoxide dismutase (SOD, malondialdehyde (MDA, and protein carbonyl (PC levels were analysed in the testicular tissues and serum. Spermatogenesis was evaluated with the Johnsen scoring system. Results. The testicular tissue and serum levels of MDA, PC, and SOD activity were increased in the obesity group in comparison to the sham operated group (P<0.05. Weight loss and melatonin treatment ameliorated MDA, PC, and SOD levels in testicular tissue and serum significantly (P<0.05. There was no significant difference between groups in terms of mean Johnsen score (P=0.727. Conclusion. Experimentally created obesity caused oxidative stress and both melatonin and weight loss reduced oxidative stress parameters in rat testes.

Intestinal metaplasia induced by x-irradiation in different strains of rats

International Nuclear Information System (INIS)

Watanabe, Hiromitsu; Naito, Masashi; Kawashima, Kengo; Ito, Akihiro

1985-01-01

Attempts were made to examine strain differences in the susceptibility of rats to intestinal metaplasia induced by X-irradiation. The gastric regions of 4 inbred male rats (SHR, F344, WKY, and LEW strains) in 5-week-old and 2 random bred male rats (SD, and WIS strains) were irradiated with a total dose of 20 Gy X-ray given in two equal fractions separated by three days. Upon sacrifice at 6 months after the last irradiation, the number of intestinal metaplastic crypts with positive reaction to alkaline phosphatase (ALP) appeared highest in the SHR and lowest in the WIS rats. Morphologically, the number of crypts with intestinal metaplasia in whole glandular stomachs of SHR, WIS, F344, and SD rats were higher than those in WKY and LEW rats. In the pyloric gland, it was highest in WIS rats, while in the fundic gland it was highest in SHR rats. The results show that the appearance and location of intestinal metaplasia by X-irradiation are greatly influenced by the strain of the rat. (author)

Vildagliptin reduces cardiac ischemic-reperfusion injury in obese orchiectomized rats.

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Pongkan, Wanpitak; Pintana, Hiranya; Jaiwongkam, Thidarat; Kredphoo, Sasiwan; Sivasinprasasn, Sivaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2016-10-01

Obesity and testosterone deprivation are associated with coronary artery disease. Testosterone and vildagliptin (dipeptidyl peptidase-4 inhibitors) exert cardioprotection during ischemic-reperfusion (I/R) injury. However, the effect of these drugs on I/R heart in a testosterone-deprived, obese, insulin-resistant model is unclear. This study investigated the effects of testosterone and vildagliptin on cardiac function, arrhythmias and the infarct size in I/R heart of testosterone-deprived rats with obese insulin resistance. Orchiectomized (O) or sham operated (S) male Wistar rats were divided into 2 groups to receive normal diet (ND) or high-fat diet (HFD) for 12 weeks. Orchiectomized rats in each diet were divided to receive testosterone (2 mg/kg), vildagliptin (3 mg/kg) or the vehicle daily for 4 weeks. Then, I/R was performed by a 30-min left anterior descending coronary artery ligation, followed by a 120-min reperfusion. LV function, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. HFD groups developed insulin resistance at week 12. At week 16, cardiac function was impaired in NDO, HFO and HFS rats, but was restored in all testosterone- and vildagliptin-treated rats. During I/R injury, arrhythmia scores, infarct size and cardiac mitochondrial dysfunction were prominently increased in NDO, HFO and HFS rats, compared with those in NDS rats. Treatment with either testosterone or vildagliptin similarly attenuated these impairments during I/R injury. These finding suggest that both testosterone replacement and vildagliptin share similar efficacy for cardioprotection during I/R injury by decreasing the infarct size and attenuating cardiac mitochondrial dysfunction caused by I/R injury in testosterone-deprived rats with obese insulin resistance. © 2016 Society for Endocrinology.

Effect of Octreotide on Hepatic Steatosis in Diet-Induced Obesity in Rats.

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Mao Li

Full Text Available Non-alcoholic fatty liver disease (NAFLD caused by liver lipid dysregulation is linked to obesity. Somatostatin (SST and its analogs have been used to treat pediatric hypothalamic obesity. However, the application of such drugs for the treatment of NAFLD has not been evaluated.This study aimed to investigate the expression levels of important regulators of hepatic lipid metabolism and the possible effect of the SST analog octreotide on these regulators.SD rats were assigned to a control group and a high-fat diet group. Obese rats from the high-fat diet group were further divided into the obese and octreotide-treated groups. The body weight, plasma SST, fasting plasma glucose (FPG, insulin, triglyceride (TG, total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C and free fatty acid (FFA levels were measured. Hepatic steatosis was evaluated based on the liver TG content, HE staining and oil red O staining. The SREBP-1c, ACC1, FAS, MTP, apoB and ADRP expression levels in the liver were also determined by RT-PCR, qRT-PCR, western blot or ELISA.The obese rats induced by high-fat diet expressed more SREBP-1c, FAS and ADRP but less MTP protein in the liver than those of control rats, whereas octreotide intervention reversed these changes and increased the level of apoB protein. Compared to the control group, obese rats showed increased liver ACC1, SREBP-1c and apoB mRNA levels, whereas octreotide-treated rats showed decreased mRNA levels of apoB and SREBP-1c. This was accompanied by increased body weight, liver TG contents, FPG, TG, TC, LDL-C, FFA, insulin and derived homeostatic model assessment (HOMA values. Octreotide intervention significantly decreased these parameters. Compared to the control group, the obese group showed a decreasing trend on plasma SST levels, which were significantly increased by the octreotide intervention.Octreotide can ameliorate hepatic steatosis in obese rats

Very low-carbohydrate versus isocaloric high-carbohydrate diet in dietary obese rats.

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Axen, Kathleen V; Axen, Kenneth

2006-08-01

The effects of a very low-carbohydrate (VLC), high-fat (HF) dietary regimen on metabolic syndrome were compared with those of an isocaloric high-carbohydrate (HC), low-fat (LF) regimen in dietary obese rats. Male Sprague-Dawley rats, made obese by 8 weeks ad libitum consumption of an HF diet, developed features of the metabolic syndrome vs. lean control (C) rats, including greater visceral, subcutaneous, and hepatic fat masses, elevated plasma cholesterol levels, impaired glucose tolerance, and fasting and post-load insulin resistance. Half of the obese rats (VLC) were then fed a popular VLC-HF diet (Weeks 9 and 10 at 5% and Weeks 11 to 14 at 15% carbohydrate), and one-half (HC) were pair-fed an HC-LF diet (Weeks 9 to 14 at 60% carbohydrate). Energy intakes of pair-fed VLC and HC rats were less than C rats throughout Weeks 9 to 14. Compared with HC rats, VLC rats exhibited impaired insulin and glycemic responses to an intraperitoneal glucose load at Week 10 and lower plasma triacylglycerol levels but retarded loss of hepatic, retroperitoneal, and total body fat at Week 14. VLC, HC, and C rats no longer differed in body weight, plasma cholesterol, glucose tolerance, or fasting insulin resistance at Week 14. Progressive decreases in fasting insulin resistance in obese groups paralleled concomitant reductions in hepatic, retroperitoneal, and total body fat. When energy intake was matched, the VLC-HF diet provided no advantage in weight loss or in improving those components of the metabolic syndrome induced by dietary obesity and may delay loss of hepatic and visceral fat as compared with an HC-LF diet.

Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats

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Lefer, D. J.; Lynch, C. D.; Lapinski, K. C.; Hutchins, P. M.

1990-01-01

Intrinsic rhythmic changes in the diameter of pial cerebral arterioles (30-70 microns) in anesthetized normotensive and hypertensive rats were assessed in vivo to determine if any significant differences exist between the two strains. All diameter measurements were analyzed using a traditional graphic analysis technique and a new frequency spectrum analysis technique known as the Prony Spectral Line Estimator. Graphic analysis of the data revealed that spontaneously hypertensive rats (SHR) possess a significantly greater fundamental frequency (5.57 +/- 0.28 cycles/min) of vasomotion compared to the control Wistar-Kyoto normotensive rats (WKY) (1.95 +/- 0.37 cycles/min). Furthermore, the SHR cerebral arterioles exhibited a significantly greater amplitude of vasomotion (10.07 +/- 0.70 microns) when compared to the WKY cerebral arterioles of the same diameter (8.10 +/- 0.70 microns). Diameter measurements processed with the Prony technique revealed that the fundamental frequency of vasomotion in SHR cerebral arterioles (6.14 +/- 0.39 cycles/min) was also significantly greater than that of the WKY cerebral arterioles (2.99 +/- 0.42 cycles/min). The mean amplitudes of vasomotion in the SHR and WKY strains obtained by the Prony analysis were found not to be statistically significant in contrast to the graphic analysis of the vasomotion amplitude of the arterioles. In addition, the Prony system was able to consistently uncover a very low frequency of vasomotion in both strains of rats that was typically less than 1 cycle/min and was not significantly different between the two strains. The amplitude of this slow frequency was also not significantly different between the two strains. The amplitude of the slow frequency of vasomotion (less than 1 cycle/min) was not different from the amplitude of the higher frequency (2-6 cycles/min) vasomotion by Prony or graphic analysis. These data suggest that a fundamental intrinsic defect exists in the spontaneously hypertensive rat

Effects of nimodipine on learning in normotensive and spontaneously hypertensive rats.

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Meneses, A; Terrón, J A; Ibarra, M; Hong, E

1997-04-01

It is well known that the calcium channel blocker, nimodipine, has beneficial effects on learning in either aged or hypertensive animals and humans. However, no attempts have been made to investigate if nimodipine can reverse the synergistic deleterious effects of aging and hypertension in the same subject. Therefore, this study investigated the effects of stable infusions of nimodipine in the autoshaping learning task using middle-aged normotensive (WKY) and hypertensive (SHR) rats. WKY and SHR of 12 months of age were implanted with osmotic minipumps releasing either vehicle or nimodipine (0.4 mg/kg/day). After 3 weeks of treatment, the animals received autoshaping training sessions during 4 consecutive days. The WKY animals treated with nimodipine exhibited the highest levels of learning during the last session, the rank order being WKY-nimodipine > SHR-nimodipine > WKY-vehicle > SHR-vehicle. These results confirm that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of both conditions, however, might produce more severe dysfunctional changes that cannot be totally reversed by nimodipine.

Roselle is cardioprotective in diet-induced obesity rat model with myocardial infarction.

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Si, Lislivia Yiang-Nee; Ali, Siti Aishah Mohd; Latip, Jalifah; Fauzi, Norsyahida Mohd; Budin, Siti Balkis; Zainalabidin, Satirah

2017-12-15

Obesity increase the risks of hypertension and myocardial infarction (MI) mediated by oxidative stress. This study was undertaken to investigate the actions of roselle aqueous extract (R) on cardiotoxicity in obese (OB) rats and thereon OB rats subjected to MI. Male Sprague-Dawley rats were fed with either normal diet or high-fat diet for 8weeks. Firstly, OB rats were divided into (1) OB and (2) OB+R (100mg/kg, p.o, 28days). Then, OB rats were subjected to MI (ISO, 85mg/kg, s.c, 2days) and divided into three groups: (1) OB+MI, (2) OB+MI+R and (3) OB+MI+enalapril for another 4weeks. Roselle ameliorated OB and OB+MI's cardiac systolic dysfunction and reduced cardiac hypertrophy and fibrosis. The increased oxidative markers and decreased antioxidant enzymes in OB and OB+MI groups were all attenuated by roselle. These observations indicate the protective effect of roselle on cardiac dysfunction in OB and OB+MI rats, which suggest its potential to be developed as a nutraceutical product for obese and obese patients with MI in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic predisposition to obesity affects behavioural traits including food reward and anxiety-like behaviour in rats.

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Vogel, Heike; Kraemer, Maria; Rabasa, Cristina; Askevik, Kaisa; Adan, Roger A H; Dickson, Suzanne L

2017-06-15

Here we sought to define behavioural traits linked to anxiety, reward, and exploration in different strains of rats commonly used in obesity research. We hypothesized that genetic variance may contribute not only to their metabolic phenotype (that is well documented) but also to the expression of these behavioural traits. Rat strains that differ in their susceptibility to develop an obese phenotype (Sprague-Dawley, Obese Prone, Obese Resistant, and Zucker rats) were exposed to a number of behavioural tests starting at the age of 8 weeks. We found a similar phenotype in the obesity susceptible models, Obese Prone and Zucker rats, with a lower locomotor activity, exploratory activity, and higher level of anxiety-like behaviour in comparison to the leaner Obese Resistant strain. We did not find evidence that rat strains with a genetic predisposition to obesity differed in their ability to experience reward from chocolate (in a condition place preference task). However, Zucker rats show higher motivated behaviour for sucrose compared to Obese Resistant rats when the effort required to obtain palatable food is relatively low. Together our data demonstrate that rat strains that differ in their genetic predisposition to develop obesity also differ in their performance in behavioural tests linked to anxiety, exploration, and reward and that these differences are independent of body weight. We conclude that genetic variations which determine body weight and the aforementioned behaviours co-exist but that future studies are required to identify whether (and which) common genes are involved. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Lean rats gained more body weight than obese ones from a high-fibre diet.

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Li, Shaoting; Zhang, Cheng; Gu, Yingyi; Chen, Long; Ou, Shiyi; Wang, Yong; Peng, Xichun

2015-10-28

There is controversy over previous findings that a high ratio of Firmicutes to Bacteriodetes helps obese animals harvest energy from the diet. To further investigate the relationship between microbial composition and energy harvest, microbial adaptation to diet and time should be considered. In this study, lean and obese rats were successfully induced with low-fat and high-fat diets. An 8-week high soyabean fibre (HSF)-containing diet was then fed to investigate the interaction between the diet and the rats' gut microbiota, as well as their influence on rats' growth. Rats' body weight (BW) was recorded weekly; their plasma lipids and their gut microbiota at week 11, 15 and 19 were analysed. After the consumption of the HSF diet, BW of lean rats increased significantly (Pcontent of plasma cholesterol was lowered and that of TAG was upgraded in both the groups when fed the HSF diet. There was no significant difference observed at each period between lean and obese rats. In the group of lean rats, the diversity of gut microbiota was elevated strongly (Pbacterial diversity and composition in obese rats were less altered after the HSF diet control. In conclusion, the increased Firmicutes and Bacteriodetes might relate to lean rats' higher BW gain; 'obese microbiota' could not help the hosts harvest more energy from the HSF diet.

Lentil-based diets attenuate hypertension and large-artery remodelling in spontaneously hypertensive rats.

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Hanson, Matthew G; Zahradka, Peter; Taylor, Carla G

2014-02-01

Hypertension is a major risk factor for CVD, the leading cause of mortality worldwide. The prevalence of hypertension is expected to continue increasing, and current pharmacological treatments cannot alleviate all the associated problems. Pulse crops have been touted as a general health food and are now being studied for their possible effects on several disease states including hypertension, obesity and diabetes. In the present study, 15-week-old spontaneously hypertensive rats (SHR) were fed diets containing 30% w/w beans, peas, lentils, chickpeas, or mixed pulses or a pulse-free control diet for 4 weeks. Normotensive Wistar-Kyoto (WKY) rats were placed on a control diet. Pulse wave velocity (PWV) was measured weekly, while blood pressure (BP) was measured at baseline and week 4. Fasting serum obtained in week 4 of the study was analysed for circulating lipids. A histological analysis was carried out on aortic sections to determine vascular geometry. Of all the pulse varieties studied, lentils were found to be able to attenuate the rise in BP in the SHR model (P< 0·05). Lentils were able to decrease the media:lumen ratio and media width of the aorta. The total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol levels of rats fed the pulse-based diets were found to be lower when compared with those of the WKY rat and SHR controls (P< 0·05). Although all pulses reduced circulating TC and LDL-C levels in the SHR, only lentils significantly reduced the rise in BP and large-artery remodelling in the SHR, but had no effect on PWV. These results indicate that the effects of lentils on arterial remodelling and BP in the SHR are independent of circulating LDL-C levels.

Herbal Formula HT048 Attenuates Diet-Induced Obesity by Improving Hepatic Lipid Metabolism and Insulin Resistance in Obese Rats

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Yoon Hee Lee

2016-10-01

Full Text Available It is well established that obesity causes a variety of chronic diseases such as cardiovascular diseases and diabetes. Despite the diligent scientific efforts to find effective ways to lower the level of obesity, the size of obese population grows continuously around the world. Here we present the results that show feeding diet containing HT048, a mixture of the extracts of Crataegus pinnatifida leaves and Citrus unshiu peel, two of the well-known traditional herbal medicines in Eastern Asia, decreases obesity in rats. We fed rats with five different diets for 10 weeks: chow diet (STD, high-fat diet (HFD, high-fat diet with 0.04% orlistat, a drug to treat obesity (HFD + Orlistat, high-fat diet with 0.2% HT048 (w/w; HFD + 0.2% HT048, and high-fat diet with 0.6% HT048 (w/w; HFD + 0.6% HT048. It was found that both body and total white adipose tissue weight of HT048 groups significantly decreased compared to those of the HFD group. Moreover, HT048 decreased serum insulin levels in HFD-fed obese rats. At the molecular level, HT048 supplementation downregulated genes involved in lipogenesis, gluconeogenesis, and adipogenesis, while the expression level of β-oxidation genes was increased. Supplementation-drug interactions are not likely as HFD and HT048-containing diet did not significantly induce genes encoding CYPs. Collectively, this study suggests that HT048 taken as dietary supplement helps to decrease obesity and insulin resistance in HFD-fed obese rats.

Changes in alanine turnover rate due to nutritional and genetic obesity in the rat.

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Yebras, M; Salvadó, J; Arola, L; Remesar, X; Segués, T

1994-08-01

The changes in alanine turnover were determined in Zucker rats, which were either genetically obese (fa/fa) or rendered obese by dietary treatment (cafeteria fed). The whole body rate of alanine turnover was higher in genetically obese rats than in rats in which obesity was induced by diet (cafeteria). This is possibly due to variations in the rate of the amino acid incorporation into proteins, since the rate of whole body alanine degradation is the same for both groups. Thus, the different pattern followed by alanine turnover rate in these types of obese animals reflects the differences in the nitrogen economy of these animals, pointing to a higher alanine utilization in the genetically obese animals and a conservative management of alanine in the cafeteria-fed animals.

LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training.

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Sriwijitkamol, Apiradee; Ivy, John L; Christ-Roberts, Christine; DeFronzo, Ralph A; Mandarino, Lawrence J; Musi, Nicolas

2006-05-01

AMPK is a key regulator of fat and carbohydrate metabolism. It has been postulated that defects in AMPK signaling could be responsible for some of the metabolic abnormalities of type 2 diabetes. In this study, we examined whether insulin-resistant obese Zucker rats have abnormalities in the AMPK pathway. We compared AMPK and ACC phosphorylation and the protein content of the upstream AMPK kinase LKB1 and the AMPK-regulated transcriptional coactivator PPARgamma coactivator-1 (PGC-1) in gastrocnemius of sedentary obese Zucker rats and sedentary lean Zucker rats. We also examined whether 7 wk of exercise training on a treadmill reversed abnormalities in the AMPK pathway in obese Zucker rats. In the obese rats, AMPK phosphorylation was reduced by 45% compared with lean rats. Protein expression of the AMPK kinase LKB1 was also reduced in the muscle from obese rats by 43%. In obese rats, phosphorylation of ACC and protein expression of PGC-1alpha, two AMPK-regulated proteins, tended to be reduced by 50 (P = 0.07) and 35% (P = 0.1), respectively. There were no differences in AMPKalpha1, -alpha2, -beta1, -beta2, and -gamma3 protein content between lean and obese rats. Training caused a 1.5-fold increase in AMPKalpha1 protein content in the obese rats, although there was no effect of training on AMPK phosphorylation and the other AMPK isoforms. Furthermore, training also significantly increased LKB1 and PGC-1alpha protein content 2.8- and 2.5-fold, respectively, in the obese rats. LKB1 protein strongly correlated with hexokinase II activity (r = 0.75, P = 0.001), citrate synthase activity (r = 0.54, P = 0.02), and PGC-1alpha protein content (r = 0.81, P < 0.001). In summary, obese insulin-resistant rodents have abnormalities in the LKB1-AMPK-PGC-1 pathway in muscle, and these abnormalities can be restored by training.

Hepatic oxidative stress, genotoxicity and vascular dysfunction in lean or obese zucker rats

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Løhr, Mille; Folkmann, Janne Kjærsgaard; Sheykhzade, Majid

2015-01-01

Metabolic syndrome is associated with increased risk of cardiovascular disease, which could be related to oxidative stress. Here, we investigated the associations between hepatic oxidative stress and vascular function in pressurized mesenteric arteries from lean and obese Zucker rats at 14, 24 an......-generated DNA damage despite substantial hepatic steatosis.......Metabolic syndrome is associated with increased risk of cardiovascular disease, which could be related to oxidative stress. Here, we investigated the associations between hepatic oxidative stress and vascular function in pressurized mesenteric arteries from lean and obese Zucker rats at 14, 24...... and 37 weeks of age. Obese Zucker rats had more hepatic fat accumulation than their lean counterparts. Nevertheless, the obese rats had unaltered age-related level of hepatic oxidatively damaged DNA in terms of formamidopyrimidine DNA glycosylase (FPG) or human oxoguanine DNA glycosylase (hOGG1...

Chronic high-sodium diet increases aortic wall endothelin-1 expression in a blood pressure-independent fashion in rats.

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Tsai, Yu-Hwai; Ohkita, Mamoru; Gariepy, Cheryl E

2006-06-01

Vascular endothelin (ET)-1 is upregulated in several forms of salt-induced hypertension. It is unclear to what extent these effects are primary or secondary to endothelial damage. We hypothesized that a high-sodium diet (HNa) increases vascular ET-1 production independent of arterial blood pressure changes. We investigated the effect of chronic HNa with and without ET(A) blockade on circulating and aortic ET-1 protein levels as well as aortic expression of ET-1 and ET(A) messenger RNA (mRNA) in inbred Wistar-Kyoto (WKY) and congenic ET(B)-deficient rats. Comparing WKY rats fed a low-sodium diet (LNa) with those fed HNa for 3 weeks, aortic wall ET-1 protein is significantly increased in response to HNa (331 +/- 43 pg/g tissue for LNa vs. 557 +/- 34 pg/gm tissue for HNa). HNa also increased aortic wall ET-1 mRNA levels by 40%, as determined by quantitative reverse transcriptase polymerase chain reaction. We then compared rats chronically treated with the ET(A)-selective antagonist, ABT-627, while receiving either LNa or HNa. There were no differences in arterial blood pressure (mean arterial pressure 89 +/- 1 mm Hg for WKY on LNa; 90 +/- 3 for WKY on HNa; 91 +/- 2 for ET(B)-deficient/ABT-627-treated on HNa) or heart rate. However, aortic wall ET-1 protein levels were 4-fold higher in the HNa group. Further, HNa increased aortic wall ET-1 mRNA (approximately 1.5- to 3-fold) and ET(A) mRNA (approximately 2- to 7-fold), independent of activation of ET(B). Therefore, the expression of ET-1 mRNA by the aortic wall is increased in response to chronic high dietary sodium in WKY rats in the absence of changes in arterial blood pressure.

The ter mutation in the rat Dnd1 gene initiates gonadal teratomas and infertility in both genders.

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Northrup, Emily; Zschemisch, Nils-Holger; Eisenblätter, Regina; Glage, Silke; Wedekind, Dirk; Cuppen, Edwin; Dorsch, Martina; Hedrich, Hans-Jürgen

2012-01-01

A spontaneous mutation leading to the formation of congenital ovarian and testicular tumors was detected in the WKY/Ztm rat strain. The histological evaluation revealed derivatives from all three germ layers, thereby identifying these tumors as teratomas. Teratocarcinogenesis was accompanied by infertility and the underlying mutation was termed ter. Linkage analysis of 58 (WKY-ter×SPRD-Cu3) F2 rats associated the ter mutation with RNO18 (LOD = 3.25). Sequencing of candidate genes detected a point mutation in exon 4 of the dead-end homolog 1 gene (Dnd1), which introduces a premature stop codon assumed to cause a truncation of the Dnd1 protein. Genotyping of the recessive ter mutation revealed a complete penetrance of teratocarcinogenesis and infertility in homozygous ter rats of both genders. Morphologically non-tumorous testes of homozygous ter males were reduced in both size and weight. This testicular malformation was linked to a lack of spermatogenesis using immunohistochemical and histological staining. Our WKY-Dnd1(ter)/Ztm rat is a novel animal model to investigate gonadal teratocarcinogenesis and the molecular mechanisms involved in germ cell development of both genders.

Cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in obese Zucker rats.

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Overton, J M; Williams, T D; Chambers, J B; Rashotte, M E

2001-04-01

The primary purpose of the study was to test the hypothesis that reduced leptin signaling is necessary to elicit the cardiovascular and metabolic responses to fasting. Lean (Fa/?; normal leptin receptor; n = 7) and obese (fa/fa; mutated leptin receptor; n = 8) Zucker rats were instrumented with telemetry transmitters and housed in metabolic chambers at 23 degrees C (12:12-h light-dark cycle) for continuous (24 h) measurement of metabolic and cardiovascular variables. Before fasting, mean arterial pressure (MAP) was higher (MAP: obese = 103 +/- 3; lean = 94 +/- 1 mmHg), whereas oxygen consumption (VO(2): obese = 16.5 +/- 0.3; lean = 18.6 +/- 0.2 ml. min(-1). kg(-0.75)) was lower in obese Zucker rats compared with their lean controls. Two days of fasting had no effect on MAP in either lean or obese Zucker rats, whereas VO(2) (obese = -3.1 +/- 0.3; lean = -2.9 +/- 0.1 ml. min(-1). kg(-0.75)) and heart rate (HR: obese = -56 +/- 4; lean = -42 +/- 4 beats/min) were decreased markedly in both groups. Fasting increased HR variability both in lean (+1.8 +/- 0.4 ms) and obese (+2.6 +/- 0.3 ms) Zucker rats. After a 6-day period of ad libitum refeeding, when all parameters had returned to near baseline levels, the cardiovascular and metabolic responses to 2 days of thermoneutrality (ambient temperature 29 degrees C) were determined. Thermoneutrality reduced VO(2) (obese = -2.4 +/- 0.2; lean = -3.3 +/- 0.2 ml. min(-1). kg(-0.75)), HR (obese = -46 +/- 5; lean = -55 +/- 4 beats/min), and MAP (obese = -13 +/- 6; lean = -10 +/- 1 mmHg) similarly in lean and obese Zucker rats. The results indicate that the cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in Zucker rats and suggest that intact leptin signaling may not be requisite for the metabolic and cardiovascular responses to reduced energy intake.

Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke

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Vitor E. Valenti

2013-06-01

Full Text Available OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY rats and spontaneously hypertensive rats (SH (16 weeks old were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V. The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm. The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus and a depressor dose of sodium nitroprusside (50 μg/kg, bolus. Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL into the 4th V. RESULTS: Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (p<0.05 to a greater extent in WKY rats exposed to sidestream cigarette smoke than in WKY rats exposed to fresh air. However, in spontaneously hypertensive rats, the effect of the catalase inhibitor treatment was stronger in the fresh air condition (p<0.05. CONCLUSION: Administration of a catalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats.

Alterations of local cerebral glucose utilization in lean and obese fa/fa rats after acute adrenalectomy.

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Doyle, P; Rohner-Jeanrenaud, F; Jeanrenaud, B

1994-08-29

An animal model often used to investigate the aetiology of obesity is the genetically obese fa/fa rat. It has many abnormalities, including hyperphagia, hyper-insulinemia, insulin resistance, low cerebral glucose utilization and an overactive hypothalamo-pituitary adrenal (HPA) axis with resulting hypercorticism. Due to the latter consideration, the aim of this work was to study the impact of acute adrenalectomy (ADX) on the local cerebral glucose utilization (LCGU) of lean and obese fa/fa rats. ADX resulted in discrete increases in LCGU of regions common to both lean and obese rats. These common regions were found to belong to be related to the limbic system. Within this system, the LCGU of the brain of obese rats was either normalized to lean sham operated values or increased by ADX to a similar degree in both groups on a percentage basis. It was concluded that the LCGU of both lean and obese animals appears to be negatively regulated, albeit to different extents, by glucocorticoids. Such negative regulation is particularly salient within the limbic system of the lean rat and even more so in the fa/fa rat. It is suggested that the long-term hypercorticism of obese fa/fa rats due to abnormal regulation of the HPA axis may result in a decreased LCGU in limbic and related regions of the brain of fa/fa rats and contribute to the expression of the obese phenotype.

The influence of sleep deprivation and obesity on DNA damage in female Zucker rats.

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Tenorio, Neuli M; Ribeiro, Daniel A; Alvarenga, Tathiana A; Fracalossi, Ana Carolina C; Carlin, Viviane; Hirotsu, Camila; Tufik, Sergio; Andersen, Monica L

2013-01-01

The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.

Corticosterone binding to tissues of adrenalectomized lean and obese Zucker rats.

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Grasa, M M; Cabot, C; Balada, F; Virgili, J; Sanchis, D; Monserrat, C; Fernández-López, J A; Remesar, X; Alemany, M

1998-12-01

The binding of corticosterone, dexamethasone and aldosterone was investigated in plasma and in homogenates of liver, kidney, brain, brown adipose tissue and visceral (periovaric) and subcutaneous white adipose tissues of Zucker lean and obese rats: intact controls, adrenalectomized and sham-operated. Corticosterone-binding globulin (CBG) accounted for most of the binding, whereas that of glucocorticoid and mineralocorticoid receptors was much lower. Plasma corticosterone levels increased in sham-operated and obviously decreased in the adrenalectomized animals. Sham-operated and adrenalectomized lean rats showed decreased plasma CBG; in the obese, CBG levels were lower than in controls and were not affected by either surgery. No variation with obesity or surgery was observed either in dexamethasone or aldosterone binding, the latter being practically zero in most samples. When expressed per unit of tissue protein, CBG activity was maximal in adipose tissues, with lowest values in brain and liver. In lean rats, tissue CBG activity decreased with either surgical treatment; no changes were observed in the obese, which also had lower CBG tissue levels. The relative lack of changes in CBG of obese rats suggests that they have lost -- at least in part -- the ability to counter-modulate the changes in glucocorticoid levels through CBG modulation, thus relying only on the control of corticosterone levels. This interpretation agrees with the postulated role of CBG modulating the availability of glucocorticoids to target cells.

Effects of early life trauma are dependent on genetic predisposition: a rat study

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Russell Vivienne A

2011-05-01

Full Text Available Abstract Background Trauma experienced early in life increases the risk of developing a number of psychological and/or behavioural disorders. It is unclear, however, how genetic predisposition to a behavioural disorder, such as attention-deficit/hyperactivity disorder (ADHD, modifies the long-term effects of early life trauma. There is substantial evidence from family and twin studies for susceptibility to ADHD being inherited, implying a strong genetic component to the disorder. In the present study we used an inbred animal model of ADHD, the spontaneously hypertensive rat (SHR, to investigate the long-term consequences of early life trauma on emotional behaviour in individuals predisposed to developing ADHD-like behaviour. Methods We applied a rodent model of early life trauma, maternal separation, to SHR and Wistar-Kyoto rats (WKY, the normotensive control strain from which SHR were originally derived. The effects of maternal separation (removal of pups from dam for 3 h/day during the first 2 weeks of life on anxiety-like behaviour (elevated-plus maze and depressive-like behaviour (forced swim test were assessed in prepubescent rats (postnatal day 28 and 31. Basal levels of plasma corticosterone were measured using radioimmunoassay. Results The effect of maternal separation on SHR and WKY differed in a number of behavioural measures. Similar to its reported effect in other rat strains, maternal separation increased the anxiety-like behaviour of WKY (decreased open arm entries but not SHR. Maternal separation increased the activity of SHR in the novel environment of the elevated plus-maze, while it decreased that of WKY. Overall, SHR showed a more active response in the elevated plus-maze and forced swim test than WKY, regardless of treatment, and were also found to have higher basal plasma corticosterone compared to WKY. Maternal separation increased basal levels of plasma corticosterone in SHR females only, possibly through adaptive

Panax ginseng Leaf Extracts Exert Anti-Obesity Effects in High-Fat Diet-Induced Obese Rats.

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Lee, Seul-Gi; Lee, Yoon-Jeong; Jang, Myeong-Hwan; Kwon, Tae-Ryong; Nam, Ju-Ock

2017-09-10

Recent studies have reported that the aerial parts of ginseng contain various saponins, which have anti-oxidative, anti-inflammatory, and anti-obesity properties similar to those of ginseng root. However, the leaf extracts of Korean ginseng have not yet been investigated. In this study, we demonstrate the anti-obesity effects of green leaf and dried leaf extracts (GL and DL, respectively) of ginseng in high-fat diet (HFD)-induced obese rats. The administration of GL and DL to HFD-induced obese rats significantly decreased body weight (by 96.5% and 96.7%, respectively), and epididymal and abdominal adipose tissue mass. Furthermore, DL inhibited the adipogenesis of 3T3-L1 adipocytes through regulation of the expression of key adipogenic regulators, such as peroxisome proliferator-activated receptor (PPAR)-γ and CCAAT/enhancer-binding protein (C/EBP)-α. In contrast, GL had little effect on the adipogenesis of 3T3-L1 adipocytes but greatly increased the protein expression of PPARγ compared with that in untreated cells. These results were not consistent with an anti-obesity effect in the animal model, which suggested that the anti-obesity effect of GL in vivo resulted from specific factors released by other organs, or from increased energy expenditure. To our knowledge, these findings are the first evidence for the anti-obesity effects of the leaf extracts of Korean ginseng in vivo.

Influence of benzodiazepines on body weight and food intake in obese and lean Zucker rats.

Science.gov (United States)

Blasi, C

2000-05-01

1. The gamma-aminobutyric acid (GABA)-ergic system, which is functionally altered in obese (fa/fa) Zucker rats, plays an important role in controlling energy balance within the central nervous system. 2. GABA receptors seem to be involved in the dysfunction of the hypothalamic energy homeostasis-controlling mechanisms in these animals due to a genetically-induced defect of the leptin-neuropeptide Y system. 3. To shed further light on the possible role played by the GABA system in the pathogenesis of this rat model, two benzodiazepine (BDZ) receptor agonists (diazepam and clonazepam) and one BDZ antagonist (flumazenil) were administered intraperitoneally in obese and lean Zucker rats. 4. Body weight gain was reduced by the BDZ agonists in both phenotypes, and one receptor-agonist (diazepam) lowered insulin concentration in obese rats. In GABA-antagonist-treated obese rats, the daily amount of body weight gain and food intake acquired an oscillatory rhythm similar to that of normal rodents. 5. By demonstrating the role of BDZ receptors, these findings may help clarify the pathophysiology of obesity and insulin resistance in fatty Zucker rats.

Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

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Kinnunen, P.; Taskinen, T.; Leppäluoto, J.; Ruskoaho, H.

1990-01-01

1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141796

Perinatal L-arginine and antioxidant supplements reduce adult blood pressure in spontaneously hypertensive rats

NARCIS (Netherlands)

Racasan, S; Braam, B; van der Giezen, DM; Goldschmeding, R; Boer, P; Koomans, HA; Joles, JA

Embryo cross-transplantation and cross-fostering between spontaneously hypertensive rats (SHR) and normotensive rats (WKY) suggest that perinatal environment modulates the genetically determined phenotype. In SHR the balance between NO and reactive oxygen species (ROS) is disturbed. We hypothesized

Effects of aerobic exercise training on cardiac renin-angiotensin system in an obese Zucker rat strain.

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Diego Lopes Mendes Barretti

Full Text Available OBJECTIVE: Obesity and renin angiotensin system (RAS hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain. METHODS: THE RATS WERE DIVIDED INTO THE FOLLOWING GROUPS: Lean Zucker rats (LZR; lean Zucker rats plus EXT (LZR+EXT; obese Zucker rats (OZR and obese Zucker rats plus EXT (OZR+EXT. EXT consisted of 10 weeks of 60-min swimming sessions, 5 days/week. At the end of the training protocol heart rate (HR, systolic blood pressure (SBP, cardiac hypertrophy (CH and function, local and systemic components of RAS were evaluated. Also, systemic glucose, triglycerides, total cholesterol and its LDL and HDL fractions were measured. RESULTS: The resting HR decreased (∼12% for both LZR+EXT and OZR+EXT. However, only the LZR+EXT reached significance (p<0.05, while a tendency was found for OZR versus OZR+EXT (p = 0.07. In addition, exercise reduced (57% triglycerides and (61% LDL in the OZR+EXT. The systemic angiotensin I-converting enzyme (ACE activity did not differ regardless of obesity and EXT, however, the OZR and OZR+EXT showed (66% and (42%, respectively, less angiotensin II (Ang II plasma concentration when compared with LZR. Furthermore, the results showed that EXT in the OZR prevented increase in CH, cardiac ACE activity, Ang II and AT2 receptor caused by obesity. In addition, exercise augmented cardiac ACE2 in both training groups. CONCLUSION: Despite the unchanged ACE and lower systemic Ang II levels in obesity, the cardiac RAS was increased in OZR and EXT in obese Zucker rats reduced some of the cardiac RAS components and prevented obesity-related CH. These results show that EXT prevented the heart RAS hyperactivity and cardiac maladaptive morphological alterations in obese Zucker rats.

Long-term characterization of the diet-induced obese and diet-resistant rat model

DEFF Research Database (Denmark)

Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel

2010-01-01

, namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization......, the results underscore the effectiveness of GLP-1 mimetics both as anti-diabetes and anti-obesity agents....

Differential responsiveness of obese (fa/fa) and lean (Fa/Fa) Zucker rats to cytokine-induced anorexia.

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Plata-Salamán, C R; Vasselli, J R; Sonti, G

1997-01-01

Pathophysiological and pharmacological concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in the cerebrospinal fluid (CSF) induce anorexia in normal rats. Obesity in humans and rodents is associated with increased TNF-alpha messenger RNA and protein levels in various cell types. This suggests that obese individuals may have differential regulation of cytokine production and dissimilar responsiveness to cytokines. In the present study, we investigated the effects of the intracerebroventricular (ICV) microinfusion of TNF-alpha (50, 100, and 500 ng/rat), IL-1 beta (1.0, 4.0, and 8.0 ng), and TNF-alpha (100 ng) plus IL-1 beta (1.0 ng) on obese (fa/fa) and lean (Fa/Fa) Zucker rats. The results show that: TNF-alpha and IL-1 beta, and the concomitant administration of TNF-alpha and IL-1 beta decreased the short-term (4 hours), nighttime (12 hours), and total daily food intakes in obese and lean rats; IL-1 beta was more potent relative to TNF-alpha; obese rats showed greater responsiveness to IL-1 beta: 8.0 ng IL-1 beta, for example, decreased the 12-hour food intake by 52% in obese and 22% in lean rats. On the other hand, obese and lean rats did not exhibit a significantly different responsiveness to the anorexia induced by 50, 100, or 500 ng TNF-alpha at the 4-hour period; and the concomitant ICV administration of TNF-alpha and IL-1 beta induced anorexia with additive (4-hour period) or synergistic (12-hour and 24-hour periods) effects in obese rats. The effect of TNF-alpha plus IL-1 beta in lean rats was greater than additive for the 12-hour and 24-hour periods. The difference in suppression of total daily food intake by TNF-alpha plus IL-1 beta in obese (-43%) versus lean (-23%) rats was significantly different (p < 0.01). The results show that obese (fa/fa) and lean (Fa/Fa) Zucker rats have differential responsiveness to the ICV microinfusion of two different classes of cytokines.

Super, Red Palm and Palm Oleins Improve the Blood Pressure, Heart Size, Aortic Media Thickness and Lipid Profile in Spontaneously Hypertensive Rats

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Boon, Chee-Meng; Ng, Mei-Han; Choo, Yuen-May; Mok, Shiueh-Lian

2013-01-01

Background Oleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension. Methodology/Principal Findings Four-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were fed 15% SO, RPO or PO supplemented diet for 15 weeks. After 15 weeks of treatment, the systolic blood pressure (SBP) of SHR treated with SO, RPO and PO were 158.4±5.0 mmHg (p<0.001), 178.9±2.7 mmHg (p<0.001) and 167.7±2.1 mmHg (p<0.001), respectively, compared with SHR controls (220.9±1.5 mmHg). Bradycardia was observed with SO and PO. In contrast, the SBP and heart rate of treated WKY rats were not different from those of WKY controls. The SO and PO significantly reduced the increased heart size and thoracic aortic media thickness observed in untreated SHR but RPO reduced only the latter. No such differences, however, were observed between the treated and untreated WKY rats. Oil Red O enface staining of thoracic-abdominal aorta did not show any lipid deposition in all treated rats. The SO and RPO significantly raised serum alkaline phosphatase levels in the SHR while body weight and renal biochemical indices were unaltered in both strains. Serum lipid profiles of treated SHR and WKY rats were unchanged, with the exception of a significant reduction in LDL-C level and total cholesterol/HDL ratio (atherogenic index) in SO and RPO treated SHR compared with untreated SHR. Conclusion The SO, RPO and PO attenuate the rise in blood pressure in SHR, accompanied by bradycardia and heart size reduction with SO and PO, and aortic media thickness reduction with SO, RPO and PO. The SO and RPO are antiatherogenic in nature by improving blood lipid profiles in SHR. PMID:23409085

The influence of sleep deprivation and obesity on DNA damage in female Zucker rats

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Neuli M. Tenorio

2013-01-01

Full Text Available OBJECTIVE: The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. METHOD: Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group. The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. RESULTS: Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. CONCLUSION: Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.

Activation of sorbitol pathway in metabolic syndrome and increased susceptibility to cataract in Wistar-Obese rats.

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Reddy, Paduru Yadagiri; Giridharan, Nappan Veettil; Reddy, Geereddy Bhanuprakash

2012-01-01

Obesity is a major public health problem worldwide, and of late, epidemiological studies indicate a preponderance of cataracts under obesity conditions. Although cataract is a multifactorial disorder and various biochemical mechanisms have been proposed, the influence of obesity on cataractogenesis has yet to be investigated. In such a scenario, a suitable animal model that develops cataract following the onset of obesity will be a welcome tool for biomedical research. Therefore, we investigated the molecular and biochemical basis for predisposition to cataract in the obese mutant rat models established in our institute because 15%-20% of these rats develop cataracts spontaneously as they reach 12-15 months of age. We analyzed the major biochemical pathways in the normal lenses of different age groups of our obese mutant rat strains, Wistar/Obese (WNIN/Ob) and WNIN/GR-Ob, the former with euglycemia and the latter with an additional impaired glucose tolerance trait. In addition, sorbitol levels were estimated in the cataractous lenses of the obese rats. Except for the polyol pathway, all the principal pathways of the lens remained unaltered. Therefore, sorbitol levels were found to be high in the normal eye lenses of obese rats (WNIN/Ob and WNIN/GR-Ob) compared to their lean controls from three months of age onwards. Between WNIN/Ob and WNIN/GR-Ob, the levels of sorbitol were higher in the latter, suggesting a synergistic effect of impaired glucose tolerance along with obesity in the activation of the sorbitol pathway. Either way, an elevated sorbitol pathway seemed to be the predisposing factor responsible for cataract formation in these mutant rats. Activation of the sorbitol pathway indeed enhances the risk of cataract development in conditions such as metabolic syndrome. These rat models thus may be valuable tools for investigating obesity-associated cataract and for developing intervention strategies, based on these findings.

Offspring predisposition to obesity due to maternal-diet-induced obesity in rats is preventable by dietary normalization before mating.

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Castro, Heriberto; Pomar, Catalina Amadora; Palou, Andreu; Picó, Catalina; Sánchez, Juana

2017-03-01

We studied in rats whether the expected detrimental effects in offspring associated to maternal dietary obesity may be reverted by obesogenic diet removal 1 month before mating. Female rats were fed a cafeteria diet (CD) from days 10 to 100 and then a standard diet (SD) (postcafeteria rats). One month after CD removal, postcafeteria rats and a group of SD-fed female rats (controls) were mated with males. At weaning, offspring were fed SD and followed until 4 months old. CD was effective at inducing obesity in dams. Its removal led to a reduction in body weight, although, after 30 days, rats retained excess body weight and fat than controls. During lactation, postcafeteria dams showed greater body fat, and higher leptin and adiponectin levels in milk than controls. From 2 months of life, offspring of postcafeteria dams displayed lower body weight than controls, with no differences in the percentage of fat, homeostatic model assessment for insulin resistance, or circulating parameters. Removal of CD in obese rats before gestation, although without complete reversion of body weight excess, may prevent the expected detrimental effects in offspring associated to an excess fat accumulation in adulthood and the related metabolic disturbances. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distribution of /sup 125/I-thyroxine in different organs and tissues of dietically obese rats

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Hartmann, K.; Voss, C.; Huebner, G. (Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic)); Weber, A. (Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic). Radiologische Klinik)

1985-04-01

The distribution of /sup 125/I-thyroxine (% dose/g tissue; tissue/plasma radioactivity ratio) was investigated in different tissues of 28-week-old obese Wistar rats. Obesity was induced by high-fat diet (HFD) and confirmed by carcass analysis; in heavy obese animals the relative and absolute fat content is increased twofold and threefold, respectively, compared to control rats fed on a low-fat diet (LFD). Heavy HFD rats exhibit diminished /sup 125/I-T/sub 4/ distribution in the 'slow pool' (fat tissue, muscle) and unchanged values in the 'fast pool' (liver, kidneys) in comparison with LFD rats with low body weight. The differences in distribution presented here are not caused by the diet per se, but they are the consequence of the obesity of the animal, because no differences in the /sup 125/I-T/sub 4/ distribution were found in the /sup 125/I-T/sub 4/ between HFD and LFD rats with relatively equal body weight and body composition. The reduced T/sub 4/ distribution in the fat tissue of obese rats is discussed in connection with possibly decreased lipolysis in this tissue and possible causal participation in the beginning of obesity.

Enhanced flavor-nutrient conditioning in obese rats on a high-fat, high-carbohydrate choice diet.

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Wald, Hallie S; Myers, Kevin P

2015-11-01

Through flavor-nutrient conditioning rats learn to prefer and increase their intake of flavors paired with rewarding, postingestive nutritional consequences. Since obesity is linked to altered experience of food reward and to perturbations of nutrient sensing, we investigated flavor-nutrient learning in rats made obese using a high fat/high carbohydrate (HFHC) choice model of diet-induced obesity (ad libitum lard and maltodextrin solution plus standard rodent chow). Forty rats were maintained on HFHC to induce substantial weight gain, and 20 were maintained on chow only (CON). Among HFHC rats, individual differences in propensity to weight gain were studied by comparing those with the highest proportional weight gain (obesity prone, OP) to those with the lowest (obesity resistant, OR). Sensitivity to postingestive food reward was tested in a flavor-nutrient conditioning protocol. To measure initial, within-meal stimulation of flavor acceptance by post-oral nutrient sensing, first, in sessions 1-3, baseline licking was measured while rats consumed grape- or cherry-flavored saccharin accompanied by intragastric (IG) water infusion. Then, in the next three test sessions they received the opposite flavor paired with 5 ml of IG 12% glucose. Finally, after additional sessions alternating between the two flavor-infusion contingencies, preference was measured in a two-bottle choice between the flavors without IG infusions. HFHC-OP rats showed stronger initial enhancement of intake in the first glucose infusion sessions than CON or HFHC-OR rats. OP rats also most strongly preferred the glucose-paired flavor in the two-bottle choice. These differences between OP versus OR and CON rats suggest that obesity is linked to responsiveness to postoral nutrient reward, consistent with the view that flavor-nutrient learning perpetuates overeating in obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

Kefir Peptides Prevent Hyperlipidemia and Obesity in High-Fat-Diet-Induced Obese Rats via Lipid Metabolism Modulation.

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Tung, Yu-Tang; Chen, Hsiao-Ling; Wu, Hsin-Shan; Ho, Mei-Hsuan; Chong, Kowit-Yu; Chen, Chuan-Mu

2018-02-01

Obesity has reached epidemic proportions worldwide. Obesity is a complex metabolic disorder that is linked to numerous serious health complications with high morbidity. The present study evaluated the effects of kefir peptides on high fat diet (HFD)-induced obesity in rats. Kefir peptides markedly improved obesity, including body weight gain, inflammatory reactions and the formation of adipose tissue fat deposits around the epididymis and kidney, and adipocyte size. Treating high fat diet (HFD)-induced obese rats with kefir peptides significantly reduced the fatty acid synthase protein and increased the p-acetyl-CoA carboxylase protein to block lipogenesis in the livers. Kefir peptides also increased fatty acid oxidation by increasing the protein expressions of phosphorylated AMP-activated protein kinase, peroxisome proliferator-activated receptor-α, and hepatic carnitine palmitoyltransferase-1 in the livers. In addition, administration of kefir peptides significantly decreased the inflammatory response (TNF-α, IL-1β, and TGF-β) to modulate oxidative damage. These results demonstrate that kefir peptides treatment improves obesity via inhibition of lipogenesis, modulation of oxidative damage, and stimulation of lipid oxidation. Therefore, kefir peptides may act as an anti-obesity agent to prevent body fat accumulation and obesity-related metabolic diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats.

Science.gov (United States)

Vollbrecht, Peter J; Nobile, Cameron W; Chadderdon, Aaron M; Jutkiewicz, Emily M; Ferrario, Carrie R

2015-12-01

Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel "junk-food" diet on the development of obesity and metabolic dysfunction, 2) over-consumption of "junk-food" in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, "junk-food" diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals. Copyright © 2015 Elsevier Inc. All rights reserved.

Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats

Science.gov (United States)

Vollbrecht, Peter J.; Nobile, Cameron W.; Chadderdon, Aaron M.; Jutkiewicz, Emily M.; Ferrario, Carrie R.

2015-01-01

Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel “junk-food” diet on the development of obesity and metabolic dysfunction, 2) over-consumption of “junk-food” in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, “junk-food” diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals. PMID:26423787

Lactobacillus paracasei HII01, xylooligosaccharides, and synbiotics reduce gut disturbance in obese rats.

Science.gov (United States)

Thiennimitr, Parameth; Yasom, Sakawdaurn; Tunapong, Wannipa; Chunchai, Titikorn; Wanchai, Keerati; Pongchaidecha, Anchalee; Lungkaphin, Anusorn; Sirilun, Sasithorn; Chaiyasut, Chaiyavat; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2018-03-20

The beneficial effects of pro-, pre-, and synbiotics on obesity with insulin resistance have been reported previously. However, the strain-specific effect of probiotics and the combination with various types of prebiotic fiber yield controversial outcomes and limit clinical applications. Our previous study demonstrated that the probiotic Lactobacillus paracasei (L. paracasei) HII01, prebiotic xylooligosaccharide (XOS), and synbiotics share similar efficacy in attenuating cardiac mitochondrial dysfunction in obese-insulin resistant rats. Nonetheless, the roles of HII01 and XOS on gut dysbiosis and gut inflammation under obese-insulin resistant conditions have not yet, to our knowledge, been investigated. Our hypothesis was that pro-, pre-, and synbiotics improve the metabolic parameters in obese-insulin resistant rats by reducing gut dysbiosis and gut inflammation. Male Wistar rats were fed with either a normal or high-fat diet that contained 19.77% and 59.28% energy from fat, respectively, for 12 wk. Then, the high-fat diet rats were fed daily with a 10 8 colony forming unit of the probiotic HII01, 10% prebiotic XOS, and synbiotics for 12 wk. The metabolic parameters, serum lipopolysaccharide levels, fecal Firmicutes/Bacteroidetes ratios, levels of Enterobacteriaceae, Bifidobacteria, and gut proinflammatory cytokine gene expression were quantified. The consumption of probiotic L. paracasei HII01, prebiotic XOS, and synbiotics for 12 wk led to a decrease in metabolic endotoxemia, gut dysbiosis (a reduction in the Firmicutes/Bacteroidetes ratio and Enterobacteriaceae), and gut inflammation in obese-insulin resistant rats. Pro-, pre-, and synbiotics reduced gut dysbiosis and gut inflammation, which lead to improvements in metabolic dysfunction in obese-insulin resistant rats. Copyright © 2018 Elsevier Inc. All rights reserved.

EXPERIMENTAL INVESTIGATION OF THE EFFECT ON THE CHEMERIN ADIPOKINE AND OBESITY OF PROBIOTIC USE IN OBESE RATS

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Mensure Nur Celik

2017-06-01

Full Text Available Chemerin is a new chemotactic protein that recently joined the adipokines family. It has been shown to play a role in adipogenesis and energy metabolism, including its role on obesity, Type 2 Diabetes Mellitus (T2DM, metabolic syndrome and cardiovascular diseases. Probiotics may play role in the prevention of obesity by various mechanisms and treatment of many diseases such as T2DM. In this study, we aimed to evaluate the effects of probiotic supplementation of chemerin adipokines on serum levels and obesity markers in obese animal models. For this purpose 3 groups of experimental animals were formed. In the obtained serum samples, the effects of probiotic supplementation on chemerin and leptin level which are indicators of obesity will be examined. Weights of all the rats in the groups were weighed each week to monitor the obesity. The weight gain in the group fed with probiotic supplementation was 10,00±27,2 g for 4 weeks and the weight gain for the group fed with high fat diet was 26,200±7,085 g (p<0.05. After 8 weeks of feding the changes of BMI values of the rats were found to be statistically significant (p<0.05. There was no significant difference between the leptin values of the groups, but the difference between the mean values of the chemerin values after 12 weeks of feeding was found to be statistically significant (p <0.05. As a result; this study showed that obese rats reduced the weight gain of probiotic supplementation without calorie restriction, positive effects on BMI and chemerin adipokine serum levels.

Effect of melatonin supplementation on pregnancy outcome in Wistar-Kyoto and Sprague-Dawley rats.

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Singh, Harbindar Jeet; Saleh, Hisham Ibrahim; Gupalo, Sergey; Omar, Effat

2013-04-25

Although melatonin supplementation is known to influence numerous physiological functions, little is however known of its effects on pregnancy outcome. This study investigated the effects of melatonin supplementation on pregnancy outcome in Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats aged 12-13 weeks. Upon confirmation of proestrus, each female rat was housed overnight with a male of the same strain. On the next morning, following confirmation of mating (vaginal smear), WKY female rats were isolated into individual metabolic cages and given 0, 25, 50 or 100 mg/kg per day of melatonin in drinking water from day 1 of pregnancy to day 21 postpartum. SD females were given 0 or 100 mg/kg per day of melatonin. Maternal weight, duration of pregnancy, litter size, birth weight and body weight of pups up to day 42, and pup mortality were recorded. Data were analyzed using ANOVA for repeated measures. Compared to controls, maternal weight gain during pregnancy was significantly lower in melatonin-supplemented dams (P melatonin-supplemented dams (P melatonin (P melatonin was significantly lower than controls (P melatonin respectively, and all pup deaths occurred after day 21 of weaning. The results suggest that melatonin supplementation during antenatal and postpartum period appears to adversely affect litter size, pup growth and mortality in WKY and SD rats. The precise mechanism causing the death is not clear.

Omega-3 Fatty Acids Supplementation Differentially Modulates the SDF-1/CXCR-4 Cell Homing Axis in Hypertensive and Normotensive Rats.

Science.gov (United States)

Halmenschlager, Luiza; Lehnen, Alexandre Machado; Marcadenti, Aline; Markoski, Melissa Medeiros

2017-08-01

We assessed the effect of acute and chronic dietary supplementation of ω-3 on lipid metabolism and cardiac regeneration, through its influence on the Stromal Derived Factor-1 (SDF-1) and its receptor (CXCR4) axis in normotensive and hypertensive rats. Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were allocated in eight groups (of eight animals each), which received daily orogastric administration of ω-3 (1 g) for 24 h, 72 h or 2 weeks. Blood samples were collected for the analysis of the lipid profile and SDF-1 systemic levels (ELISA). At the end of the treatment period, cardiac tissue was collected for CXCR4 expression analysis (Western blot). The use of ω-3 caused a reduction in total cholesterol levels ( p = 0.044), and acutely activated the SDF-1/CXCR4 axis in normotensive animals ( p = 0.037). In the presence of the ω-3, after 72 h, SDF-1 levels decreased in WKY and increased in SHR ( p = 0.017), and tissue expression of the receptor CXCR4 was higher in WKY than in SHR ( p = 0.001). The ω-3 fatty acid supplementation differentially modulates cell homing mediators in normotensive and hypertensive animals. While WKY rats respond acutely to omega-3 supplementation, showing increased release of SDF-1 and CXCR4, SHR exhibit a weaker, delayed response.

Vitamin D3 deficiency increases DNA damage and modify the expression of genes associated with hypertension in normotensive and hypertensive rats

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Carla Silva Machado

2015-05-01

Full Text Available Vitamin D3 is a lipophilic micronutrient obtained from the diet (salmon, sardines, mackerel and cod liver oil or by the conversion of 7-dehydrocholesterol on skin after exposure to UVB radiation. This vitamin participates in several cellular processes, contributes to the maintenance of calcium concentrations, acts on phosphorus absorption, and is also related to the development and progression of chronic diseases. In hypertension, it is known that vitamin D3 act on renin-angiotensin-aldosterone system, regulates the gene expression and can induce or attenuate oxidative DNA damage. Vitamin D3 deficiency is present in 30-50% of human population (Pilz et al., 2009, and has been associated with increase of chromosomal instability and DNA damage (Nair-Shalliker; Armstrong; Fenech, 2012. Since experimental and clinical studies have suggested a relationship between vitamin D3 and blood pressure, the aim of this study was to evaluate whether vitamin D3 deficiency or supplementation lead to an increase or decrease in DNA damage, regulates the expression of genes associated with hypertension and changes the systolic blood pressure. Spontaneously hypertensive rats (SHR, used as a model of human essential hypertension, and their normotensive controls (Wistar Kyoto – WKY were fed a control diet (vitamin D3 at 1.000 UI/kg, a deficient diet (vitamin D3 at 0 UI/kg or a supplemented diet (vitamin D3 at 10.000 UI/kg for 12 weeks. DNA damage was assessed by comet assay in cardiac muscle tissue and blood tissue, following the methodology proposed by Singh et al. (1988 and Tice et al. (2000; gene expression of 84 genes was assessed by RT2ProfilerTM PCR Array in cardiac muscle tissue; and systolic blood pressure was measured weekly by a noninvasive method using tail plethysmography. In SHR and WKY rats, vitamin D3 deficiency increased DNA damage in the blood tissue and did not change the DNA damage in cardiac muscle tissue; vitamin D3 supplementation maintained the

Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats

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Schwartz, M.W.; Figlewicz, D.F.; Kahn, S.E.; Baskin, D.G.; Greenwood, M.R.; Porte, D. Jr.

1990-01-01

In order to study the role of plasma insulin in regulating the binding of insulin to the endothelium of the blood-brain barrier (BBB), insulin binding to a purified preparation of brain capillaries was measured in both genetically obese Zucker rats and lean Zucker controls. We found a reduction of 65% in brain capillary insulin binding site number in the obese compared to lean rats with no change in receptor affinity. Furthermore, specific insulin binding to brain capillaries was negatively correlated (p less than 0.05) to the plasma insulin level, suggesting a role for plasma insulin in regulating insulin binding. A similar relationship was observed between insulin receptor number in liver membranes and the plasma insulin level. We conclude that obese, hyperinsulinemic Zucker rats exhibit a reduction in the number of BBB insulin receptors, which parallels the reduction seen in other peripheral tissues. Since insulin receptors have been hypothesized to participate in the transport of insulin across the BBB, the reduction observed in the obese rats may account for the decrease in cerebrospinal fluid insulin uptake previously demonstrated in these animals

Impulsive-choice patterns for food in genetically lean and obese Zucker rats.

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Boomhower, Steven R; Rasmussen, Erin B; Doherty, Tiffany S

2013-03-15

Behavioral-economic studies have shown that differences between lean and obese Zuckers in food consumption depend on the response requirement for food. Since a response requirement inherently increases the delay to reinforcement, differences in sensitivity to delay may also be a relevant mechanism of food consumption in the obese Zucker rat. Furthermore, the endocannabinoid neurotransmitter system has been implicated in impulsivity, but studies that attempt to characterize the effects of cannabinoid drugs (e.g., rimonabant) on impulsive choice may be limited by floor effects. The present study aimed to characterize impulsive-choice patterns for sucrose using an adjusting-delay procedure in genetically lean and obese Zuckers. Ten lean and ten obese Zucker rats chose between one lever that resulted in one pellet after a standard delay (either 1 s or 5 s) and a second lever that resulted in two or three pellets after an adjusting delay. After behavior stabilized under baseline, rimonabant (0-10 mg/kg) was administered prior to some choice sessions in the two-pellet condition. Under baseline, obese Zuckers made more impulsive choices than leans in three of the four standard-delay/pellet conditions. Additionally, in the 2-pellet condition, rimonabant increased impulsive choice in lean rats in the 1-s standard-delay condition; however, rimonabant decreased impulsive choice in obese rats in the 1-s and 5-s standard-delay conditions. These data suggest that genetic factors that influence impulsive choice are stronger in some choice conditions than others, and that the endocannabinoid system may be a relevant neuromechanism. Copyright © 2012 Elsevier B.V. All rights reserved.

Antiobesity, antioxidant and antidiabetic activities of red Ginseng plant extract in obese diabetic rats

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Mostafa Abbas Shalaby

2013-06-01

Full Text Available Aim: This study aimed to investigate the effects of red ginseng extract (RGE on adiposity index, some serum biochemical parameters and tissue antioxidant activity in obese diabetic rats. Materials and Methods: Five groups of male Sprague-Dawley rats were used. Group (1 was negative control and the other 4 groups were fed on high fat-diet for 6 weeks to induce obesity. The obese rats were then rendered diabetic by intraperitoneal injection of alloxan for 5 days. Group (2 was kept obese diabetic (positive control and the other 3 groups were orally given RGE at 100, 200 and 400 mg /kg /day, respectively, for 4 weeks. Blood samples were collected for biochemical analyses and kidneys were taken to assay of activities of antioxidant enzymes. Results: oral dosage of RGE to obese diabetic rats significantly (P < 0.05 reduced adiposity index; decreased serum levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, gamma- glutamyl transpeptidase (GGT enzymes, total cholesterol (TC, triglycerides (TG, and low density lipoproteins (LDL-c and improved atherogenic index. Blood glucose and leptin hormone decreased, but insulin increased by administration of RGE. it increased activities of superoxide dismutase (SOD, glutathione peroxidase (GPx and catalase (CAT antioxidant enzymes in kidneys tissues. Conclusion: Red ginseng extract produces antiobesity, antioxidant, and antidiabetic activities in obese diabetic rats. The study suggests that red ginseng plant may be beneficial for the treatment of patients who suffer from obesity associated with diabetes. [J Intercult Ethnopharmacol 2013; 2(3.000: 165-172

Treatment with low-dose resveratrol reverses cardiac impairment in obese prone but not in obese resistant rats.

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Louis, Xavier L; Thandapilly, Sijo J; MohanKumar, Suresh K; Yu, Liping; Taylor, Carla G; Zahradka, Peter; Netticadan, Thomas

2012-09-01

We hypothesized that a low-dose resveratrol will reverse cardiovascular abnormalities in rats fed a high-fat (HF) diet. Obese prone (OP) and obese resistant (OR) rats were fed an HF diet for 17 weeks; Sprague-Dawley rats fed laboratory chow served as control animals. During the last 5 weeks of study, treatment group received resveratrol daily by oral gavage at a dosage of 2.5 mg/kg body weight. Assessments included echocardiography, blood pressure, adiposity, glycemia, insulinemia, lipidemia, and inflammatory and oxidative stress markers. Body weight and adiposity were significantly higher in OP rats when compared to OR rats. Echocardiographic measurements showed prolonged isovolumic relaxation time in HF-fed OP and OR rats. Treatment with resveratrol significantly improved diastolic function in OP but not in OR rats without affecting adiposity. OP and OR rats had increased blood pressure which remained unchanged with treatment. OP rats had elevated fasting serum glucose and insulin, whereas OR rats had increased serum glucose and normal insulin concentrations. Resveratrol treatment significantly reduced serum glucose while increasing serum insulin in both OP and OR rats. Inflammatory and oxidative stress markers, serum triglycerides and low-density lipoprotein were higher in OP rats, which were significantly reduced with treatment. In conclusion, HF induced cardiac dysfunction in both OP and OR rats. Treatment reversed abnormalities in diastolic heart function associated with HF feeding in OP rats, but not in OR rats. The beneficial effects of resveratrol may be mediated through regression of hyperglycemia, oxidative stress and inflammation. Copyright © 2012 Elsevier Inc. All rights reserved.

Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats.

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Potikanond, Saranyapin; Rattanachote, Pinyada; Pintana, Hiranya; Suntornsaratoon, Panan; Charoenphandhu, Narattaphol; Chattipakorn, Nipon; Chattipakorn, Siriporn

2016-02-01

The present study aimed to test the hypothesis that testosterone deprivation impairs osteoblastic insulin signaling, decreases osteoblast survival, reduces bone density, and that obesity aggravates those deleterious effects in testosterone-deprived rats. Twenty four male Wistar rats underwent either a bilateral orchiectomy (O, n=12) or a sham operation (S, n=12). Then the rats in each group were further divided into two subgroups fed with either a normal diet (ND) or a high-fat diet (HF) for 12 weeks. At the end of the protocol, blood samples were collected to determine metabolic parameters and osteocalcin ratios. The tibiae were collected to determine bone mass using microcomputed tomography and for osteoblast isolation. The results showed that rats fed with HF (sham-operated HF-fed rats (HFS) and ORX HF-fed rats (HFO)) developed peripheral insulin resistance and had decreased trabecular bone density. In ND-fed rats, only the ORX ND-fed rats (NDO) group had decreased trabecular bone density. In addition, osteoblastic insulin resistance, as indicated by a decrease in tyrosine phosphorylation of the insulin receptor and Akt, were observed in all groups except the sham-operated ND-fed rats (NDS) rats. Those groups, again with the exception of the NDS rats, also had decreased osteoblastic survival. No differences in the levels of osteoblastic insulin resistance and osteoblastic survival were found among the NDO, HFS, and HFO groups. These findings suggest that either testosterone deprivation or obesity alone can impair osteoblastic insulin signaling and decrease osteoblastic survival leading to the development of osteoporosis. However, obesity does not aggravate those deleterious effects in the bone of testosterone-deprived rats. © 2016 Society for Endocrinology.

Prevention of diet-induced obesity in rats by oral application of collagen fragments

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Raksha Nataliia G.

2018-01-01

Full Text Available The aim of the present study was to determine whether orally applied collagen fragments (CFs could affect the development of obesity in obese rats. To this end, experimental rats that were exposed to a high-calorie diet (HCD for four weeks were randomly divided into two groups: HCD and HCD+CFs, with both groups continuing to receive the HCD. However, rats from the HCD+CFs group were also provided with CFs in a 0.05-M citrate buffer (pH 5.0 (1 g·kg-1 of body weight by intragastric administration, every other day for the next six weeks. Selected parameters associated with obesity development and insulin resistance, as well as serum markers of oxidative stress and the cytokine profile were assessed at the end of the 10th week. Supplementation with CFs resulted in a decrease in body weight and body mass index when compared to animals exposed to a HCD. The observed changes were assumed to be caused by a lower food intake and increased water intake by obese rats treated with CFs. Enhanced activity of superoxide dismutase (SOD, catalase (CAT and decreased malondialdehyde (MDA concentration were detected in the HCD+CF group of animals when compared to untreated HCD-fed rats. Administration of CFs also lowered the serum concentrations of the proinflammatory cytokines IL-1β and IL-12, whereas the concentration of the anti-inflammatory cytokine IL-10 was significantly increased and the concentration of cytokine IL-4 was near the control value. Decreased concentrations of fasting blood glucose, glycated hemoglobin (GHbA1c and serum insulin and increased tolerance to glucose in the oral glucose tolerance test (OGTT were observed in the HCD+CF group of animals when compared to rats in the HCD group. We concluded that CFs mediated a therapeutic effect on obesity development in rats exposed to a HCD by affecting pathways involved in obesity pathogenesis.

Inhalation of Roman chamomile essential oil attenuates depressive-like behaviors in Wistar Kyoto rats.

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Kong, Yingying; Wang, Ting; Wang, Rong; Ma, Yichuan; Song, Shanshan; Liu, Juan; Hu, Weiwei; Li, Shengtian

2017-06-01

The idea of aromatherapy, using essential oils, has been considered as an alternative antidepressant treatment. In the present study, we investigated the effect of Roman chamomile essential oil inhalation for two weeks on depressive-like behaviors in Wistar-Kyoto (WKY) rats. We found that inhalation of either Roman chamomile or one of its main components α-pinene, attenuated depressive-like behavior in WKY rats in the forced swim test. Using isobaric tags for relative and absolute quantitation analysis (iTRAQ), we found that inhalation of α-pinene increased expression of proteins that are involved in oxidative phosphorylation, such as cytochrome c oxidase subunit 6C-2, cytochrome c oxidase subunit 7A2, ATPase inhibitor in the hippocampus, and cytochrome c oxidase subunit 6C-2, ATP synthase subunit e, Acyl carrier protein, and Cytochrome b-c1 complex subunit 6 in the PFC (prefrontal cortex). In addition, using the quantitative real-time polymerase chain reaction technique, we confirmed an increase of parvalbumin mRNA expression in the hippocampus, which was shown to be upregulated by 2.8-fold in iTRAQ analysis, in α-pinene treated WKY rats. These findings collectively suggest the involvement of mitochondrial functions and parvalbumin-related signaling in the antidepressant effect of α-pinene inhalation.

Unprovoked atrial tachyarrhythmias in aging spontaneously hypertensive rats: the role of the autonomic nervous system.

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Scridon, Alina; Gallet, Clément; Arisha, Moussa M; Oréa, Valérie; Chapuis, Bruno; Li, Na; Tabib, Alain; Christé, Georges; Barrès, Christian; Julien, Claude; Chevalier, Philippe

2012-08-01

Experimental models of unprovoked atrial tachyarrhythmias (AT) in conscious, ambulatory animals are lacking. We hypothesized that the aging, spontaneously hypertensive rat (SHR) may provide such a model. Baseline ECG recordings were acquired with radiotelemetry in eight young (14-wk-old) and eight aging (55-wk-old) SHRs and in two groups of four age-matched Wistar-Kyoto (WKY) rats. Quantification of AT and heart rate variability (HRV) analysis were performed based on 24-h ECG recordings in unrestrained rats. All animals were submitted to an emotional stress protocol (air-jet). In SHRs, carbamylcholine injections were also performed. Spontaneous AT episodes were observed in all eight aging SHRs (median, 91.5; range, 4-444 episodes/24 h), but not in young SHRs or WKY rats. HRV analysis demonstrated significantly decreased low frequency components in aging SHRs compared with age-matched WKY rats (P aging (P = 0.01) SHRs compared with normotensive controls. In aging SHRs, emotional stress significantly reduced the number of arrhythmic events, whereas carbamylcholine triggered AT and significantly increased atrial electrical instability. This study reports the occurrence of unprovoked episodes of atrial arrhythmia in hypertensive rats, and their increased incidence with aging. Our results suggest that autonomic imbalance with relative vagal hyperactivity may be responsible for the increased atrial arrhythmogenicity observed in this model. We also provide evidence that, in this model, the sympatho-vagal imbalance preceded the occurrence of arrhythmia. These results indicate that aging SHRs may provide valuable insight into the understanding of atrial arrhythmias.

Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

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Suhana Samat

2017-01-01

Full Text Available Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats.

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Samat, Suhana; Kanyan Enchang, Francis; Nor Hussein, Fuzina; Wan Ismail, Wan Iryani

2017-01-01

Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

Obesity decreases the oxidant stress induced by tobacco smoke in a rat model.

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Montaño, Martha; Pérez-Ramos, J; Esquivel, A; Rivera-Rosales, R; González-Avila, G; Becerril, C; Checa, M; Ramos, C

2016-09-01

Obesity and emphysema are associated with low-grade systemic inflammation and oxidant stress. Assuming that the oxidant stress induced by emphysema would be decreased by obesity, we analyzed the oxidant/antioxidant state in a rat model combining both diseases simultaneously. Obesity was induced using sucrose, while emphysema by exposure to tobacco smoke. End-points evaluated were: body weight, abdominal fat, plasma dyslipidemia and malondialdehyde (MDA), insulin and glucose AUC, activities of Mn-superoxide dismutase (Mn-SOD), glutathione reductase (GR), glutathione transferase (GST) and glutathione peroxidase (GPx); lung MnSOD and 3-nitrotyrosine (3-NT) immunostaining, and expression of αV and β6 integrin subunits. In rats with obesity, the body weight, abdominal fat, plasma triglyceride levels, glucose AUC, insulin levels, GST activity, and αV and β6 integrin expressions were amplified. The rats with emphysema had lower values of body weight, abdominal fat, plasma insulin, triglycerides and glucose AUC but higher values of plasma MDA, GPx activity, and the lung expression of the αV and β6 integrins. The combination of obesity and emphysema compared to either condition alone led to diminished body weight, abdominal fat, plasma insulin MDA levels, GPx and GST activities, and αV and β6 integrin expressions; these parameters were all previously increased by obesity. Immunostaining for MnSOD augmented in all experimental groups, but the staining for 3-NT only increased in rats treated with tobacco alone or combined with sucrose. Results showed that obesity reduces oxidant stress and integrin expression, increasing antioxidant enzyme activities; these changes seem to partly contribute to a protective mechanism of obesity against emphysema development.

Effects of 2-AG on the reinforcing properties of wheel activity in obese and lean Zucker rats.

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Smith, Shilo L; Rasmussen, Erin B

2010-07-01

The endocannabinoid system plays a role in obesity, primarily by its role in food reward. Activity, also involved in obesity, seems to be at least partially controlled by the endocannabinoid system, but the relevant behavioral and neurochemical mechanisms have not been well established. This study represents an attempt to begin elucidating these mechanisms by examining the effects of an endogenous cannabinoid ligand, 2-arachidonoylglycerol (2-AG), on the reinforcing properties of exercise reinforcement in lean and obese Zucker rats. Ten obese and 10 lean Zucker rats pressed a locked door under a progressive ratio schedule of reinforcement that, when unlocked, provided access to a running wheel for 2-min periods. After baseline breakpoints were established, doses of 2-AG (0.3-3 mg/kg) were administered before experimental sessions. Obese rats exhibited lower breakpoints for wheel activity, lower response rates, and fewer revolutions compared with lean rats. 2-AG decreased breakpoints, response rates, and revolutions for obese rats, and revolutions only for lean rats. These data suggest that 2-AG may reduce the reinforcing properties of activity, and that obese Zuckers may show a greater sensitivity to 2-AG. The data also suggest that endocannabinoids may play a role in the reinforcing properties of exercise.

Eucommia leaf extract (ELE) prevents OVX-induced osteoporosis and obesity in rats.

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Zhang, Wenping; Fujikawa, Takahiko; Mizuno, Kaito; Ishida, Torao; Ooi, Kazuya; Hirata, Tetsuya; Wada, Atsunori

2012-01-01

The cortex of Eucommia ulmoides Oliver is widely used to treat kidney deficiency in traditional Chinese medicine. Its leaves have recently been reported to have anti-obesity properties in metabolic syndrome-like rat models. Due to a sharp decline in estrogen production, obesity, together with osteoporosis, are common problems in postmenopausal women. In this study, we examined the potential effect of Eucommia leaf extract (ELE) in preventing osteoporosis and obesity induced by ovariectomy (OVX). Forty-six female Wistar rats were divided into six groups: Sham-Cont, OVX-Cont, and four OVX groups administered estradiol and different concentrations of ELE 1.25%, ELE 2.5%, and ELE 5%. Treatments were administered after ovariectomy at six weeks of age and continued for 12 weeks. OVX induced a significant decrease in the bone mineral density (BMD) of the lumbar, femora, and tibiae, together with a marked increase in body mass index (BMI). The administration of 5% ELE led to a significant increase in tibial and femoral BMD, as well as significantly increased bone-strength parameters when compared with OVX-Cont rats. According to the suppressed Dpd and increased osteocalcin concentrations in ELE 5% rats, we suggest that varying proportions of bone formation and bone absorption contributed to the enhanced BMD in the femora and tibiae. In addition, significant decreases in body weight, BMI and fat tissue in 5% ELE rats were also observed. These results suggest that ELE may have curative properties for BMD and BMI in OVX rats, and could provide an alternative therapy for the prevention of both postmenopausal osteoporosis and obesity.

Increased in vivo glucose utilization in 30-day-old obese Zucker rat: Role of white adipose tissue

International Nuclear Information System (INIS)

Krief, S.; Bazin, R.; Dupuy, F.; Lavau, M.

1988-01-01

In vivo whole-body glucose utilization and uptake in multiple individual tissues were investigated in conscious 30-day-old Zucker rats, which when obese are hyperphagic, hyperinsulinemic, and normoglycemic. Whole-body glucose metabolism (assessed by [3- 3 H]glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia. In obese compared with lean rats, tissue glucose uptake was increased by 15, 12, and 6 times in dorsal, inguinal, perigonadal white depots, respectively; multiplied by 2.5 in brown adipose tissue; increased by 50% in skin from inguinal region but not in that from cranial, thoracic, or dorsal area; and increased twofold in diaphragm but similar in heart in proximal intestine, and in total muscular mass of limbs. The data establish that in young obese rats the hypertrophied white adipose tissue was a major glucose-utilizing tissue whose capacity for glucose disposal compared with that of half the muscular mass. Adipose tissue could therefore play an important role in the homeostasis of glucose in obese rats in the face of their increased carbohydrate intake

Activity of thyroxine 5' deiodinase in brown fat of lean and obese zucker rats

International Nuclear Information System (INIS)

Wu, S.Y.; Fisher, D.A.; Stern, J.S.; Glick, Z.

1986-01-01

This study examines the possibility that the reduced brown adipose tissue (BAT) thermogenesis in the Zucker obese rat may result from a limited capacity for conversion of T 4 to T 3 in BAT, through activity of T 4 5' deiodinase. Eighteen lean (Fa/.) and 18 age matched obese (fa/fa), about 16 weeks old, were each divided into 3 groups (n=6 per group). Group 1 and 2 were fed Purina Rat Chow and a cafeteria diet respectively for 21 days, and maintained at 22 0 C+/-2. Group 3 was fed rat chow and maintained at 8 0 C+/-1 for 7 days. Activity of T 4 5'deiodinase was determined in vitro. T 3 was measured by a radioimmunoassay. The rate of T 4 to T 3 conversion was similar in the lean and the obese rats maintained at room temperature, whether fed rat chow or a cafeteria diet (about 40 to 50 pmol T 3 /scapular BAT depot, per hour). However, lean rats exposed to the cold displayed about a 5 fold increase in T 4 5' deiodinase activity (p 3 may account for the reduced tolerance of obese animals to cold, but it does not account for their reduced diet induced BAT thermogenesis

Super, red palm and palm oleins improve the blood pressure, heart size, aortic media thickness and lipid profile in spontaneously hypertensive rats.

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Boon, Chee-Meng; Ng, Mei-Han; Choo, Yuen-May; Mok, Shiueh-Lian

2013-01-01

Oleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension. Four-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were fed 15% SO, RPO or PO supplemented diet for 15 weeks. After 15 weeks of treatment, the systolic blood pressure (SBP) of SHR treated with SO, RPO and PO were 158.4±5.0 mmHg (prats were not different from those of WKY controls. The SO and PO significantly reduced the increased heart size and thoracic aortic media thickness observed in untreated SHR but RPO reduced only the latter. No such differences, however, were observed between the treated and untreated WKY rats. Oil Red O enface staining of thoracic-abdominal aorta did not show any lipid deposition in all treated rats. The SO and RPO significantly raised serum alkaline phosphatase levels in the SHR while body weight and renal biochemical indices were unaltered in both strains. Serum lipid profiles of treated SHR and WKY rats were unchanged, with the exception of a significant reduction in LDL-C level and total cholesterol/HDL ratio (atherogenic index) in SO and RPO treated SHR compared with untreated SHR. The SO, RPO and PO attenuate the rise in blood pressure in SHR, accompanied by bradycardia and heart size reduction with SO and PO, and aortic media thickness reduction with SO, RPO and PO. The SO and RPO are antiatherogenic in nature by improving blood lipid profiles in SHR.

Sibutramine reduces feeding, body fat and improves insulin resistance in dietary-obese male Wistar rats independently of hypothalamic neuropeptide Y

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Brown, Michael; Bing, Chen; King, Peter; Pickavance, Lucy; Heal, David; Wilding, John

2001-01-01

We studied the effects of the novel noradrenaline and serotonin (5-HT) reuptake inhibitor sibutramine on feeding and body weight in a rat model of dietary obesity, and whether it interacts with hypothalamic neuropeptide Y (NPY) neurones.Chow-fed and dietary-obese (DIO) male Wistar rats were given sibutramine (3 mg kg−1 day−1 p.o.) or deionized water for 21 days.Sibutramine decreased food intake throughout the treatment period in both dietary-obese rats (Psibutramine-treated dietary-obese rats (Psibutramine treatment (Psibutramine compared to untreated controls.The hypophagic and anti-obesity effects of sibutramine in dietary-obese Wistar rats appear not to be mediated by inhibition of ARC NPY neurones. PMID:11309262

Blood Pressure Interventions Affect Acute and Four-Week Diesel Exhaust Induced Pulmonary Injury in Healthy and Hypertensive Rats

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Rationale: We recently showed that inhalation exposure of normotensive Wistar Kyoto (WKY) rats to whole diesel exhaust (DE) elicits changes in cardiac gene expression that broadly mimics expression in spontaneously hypertensive (SH) rats without DE. We hypothesized that pharmacol...

Milk improved the metabolic syndrome in obese ß rats

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María Catalina Olguin

2014-02-01

Full Text Available The response of adult spontaneously obese rats from the IIMb/Beta strain fed a high calcium skimmed milk diet (MHCa, high calcium from carbonate (HCa and a normal AIN 93 diet during 45 days was evaluated. Body weight, food intake and fecal fat excretion were measured. At the end of the experiment rats were euthanized, abdominal fat pads and livers were excised and weighed. Blood and liver triacylglycerols, total cholesterol and fractions were quantified. Body weight increase and abdominal fat pads in the MHCa group were significantly lower than in the other two. Plasma triacylglycerols, total and LDL-cholesterol were diminished in the MHCa group. Fecal lipid excretion was increased in the adult MHCa group. Total liver lipids and triacylglycerols showed a significant diminution in the MHCa group. These results suggest that calcium and other bioactive compounds from milk, most probably present in whey fraction, and not calcium carbonate exerted an "anti-obesity" effect on these rats.

Cereal based diets modulate some markers of oxidative stress and inflammation in lean and obese Zucker rats

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Mano Mark

2011-05-01

Full Text Available Abstract Background The potential of cereals with high antioxidant capacity for reducing oxidative stress and inflammation in obesity is unknown. This study investigated the impact of wheat bran, barley or a control diet (α-cellulose on the development of oxidative stress and inflammation in lean and obese Zucker rats. Methods Seven wk old, lean and obese male Zucker rats (n = 8/group were fed diets that contained wheat bran, barley or α-cellulose (control. After 3 months on these diets, systolic blood pressure was measured and plasma was analysed for glucose, insulin, lipids, oxygen radical absorbance capacity (ORAC, malondialdehyde, glutathione peroxidase and adipokine concentration (leptin, adiponectin, interleukin (IL-1β, IL-6, TNFα, plasminogen activator inhibitor (PAI-1, monocyte chemotactic protein (MCP-1. Adipokine secretion rates from visceral and subcutaneous adipose tissue explants were also determined. Results Obese rats had higher body weight, systolic blood pressure and fasting blood lipids, glucose, insulin, leptin and IL-1β in comparison to lean rats, and these measures were not reduced by consumption of wheat bran or barley based diets. Serum ORAC tended to be higher in obese rats fed wheat bran and barley in comparison to control (p = 0.06. Obese rats had higher plasma malondialdehyde (p Conclusions A 3-month dietary intervention was sufficient for Zucker obese rats to develop oxidative stress and systemic inflammation. Cereal-based diets with moderate and high antioxidant capacity elicited modest improvements in indices of oxidative stress and inflammation.

Differential effects of a selective dopamine D1-like receptor agonist on motor activity and c-fos expression in the frontal-striatal circuitry of SHR and Wistar-Kyoto rats

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Diaz Heijtz Rochellys

2006-05-01

Full Text Available Abstract Background Molecular genetic studies suggest the dopamine D1 receptor (D1R may be implicated in attention-deficit/hyperactivity disorder (ADHD. As little is known about the potential motor role of D1R in ADHD, animal models may provide important insights into this issue. Methods We investigated the effects of a full and selective D1R agonist, SKF-81297 (0.3, 3 and 10 mg/kg, on motor behaviour and expression of the plasticity-associated gene, c-fos, in habituated young adult male Spontaneously Hypertensive Rats (SHR, the most commonly used animal model of ADHD, and Wistar-Kyoto (WKY; the strain from which SHR were derived. Results SHR rats were more behaviourally active than WKY rats after injection with vehicle. The 0.3 mg/kg dose of SKF-81297 increased motor behaviour (locomotion, sifting, rearing, and sniffing in both SHR and WKY rats. Total grooming was also stimulated, but only in WKY rats. The same dose increased c-fos mRNA expression in the piriform cortex of both strains. The 3 mg/kg dose increased sifting and sniffing in both strains. Locomotion was also stimulated towards the end of the testing period. The intermediate dose decreased total rearing in both strains, and produced a significant increase in c-fos mRNA in the striatum, nucleus accumbens, olfactory tuberculum, and in the cingulate, agranular insular and piriform cortices. The 10 mg/kg dose of SKF-81297 produced a biphasic effect on locomotion, which was characterized by an initial decrease followed by later stimulation. The latter stimulatory effect was more pronounced in SHR than in WKY rats when compared to their respective vehicle-injected groups. The 10 mg/kg dose also stimulated sifting and sniffing in both strains. Both the 3 and 10 mg/kg doses had no effect on total grooming. The 10 mg/kg dose induced significantly higher levels of c-fos mRNA expression in the nucleus accumbens and adjacent cortical regions (but not striatum of SHR when compared to WKY rats

Differential use of danger and safety signals in an animal model of anxiety vulnerability: The behavioral economics of avoidance.

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Spiegler, Kevin M; Fortress, Ashley M; Pang, Kevin C H

2018-03-02

Differential processing of danger and safety signals may underlie symptoms of anxiety disorders and posttraumatic stress disorder. One symptom common to these disorders is pathological avoidance. The present study examined whether danger and safety signals influence avoidance differently in anxiety-vulnerable Wistar-Kyoto (WKY) rats and Sprague Dawley (SD) rats. SD and WKY rats were tested in a novel progressive ratio avoidance task with and without danger or safety signals. Two components of reinforcement, hedonic value and motivation, were determined by fitting an exponentiated demand equation to the data. Hedonic value of avoidance did not differ between SD and WKY rats, but WKY rats had greater motivation to avoid than SD rats. Removal of the safety signal reduced motivation to avoid in SD, but not WKY, rats. Removal of the danger signal did not alter avoidance in either strain. When danger and safety signals were presented simultaneously, WKY rats responded to the danger signals, whereas SD rats responded to the safety signal. The results provide evidence that 1) safety signals enhance motivation to avoid in SD rats, 2) both danger and safety signals influence motivation in WKY rats, and 3) danger signals take precedence over safety signals when presented simultaneously in WKY rats. Thus, anxiety vulnerability is associated with preferential use of danger signals to motivate avoidance. The differential use of danger and safety signals has important implications for the etiology and treatment of pathological avoidance in anxiety disorders and posttraumatic stress disorder. Copyright © 2017. Published by Elsevier Inc.

Moderately Low Magnesium Intake Impairs Growth of Lean Body Mass in Obese-Prone and Obese-Resistant Rats Fed a High-Energy Diet

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Jesse Bertinato

2016-04-01

Full Text Available The physical and biochemical changes resulting from moderately low magnesium (Mg intake are not fully understood. Obesity and associated co-morbidities affect Mg metabolism and may exacerbate Mg deficiency and physiological effects. Male rats selectively bred for diet-induced obesity (OP, obese-prone or resistance (OR, obese-resistant were fed a high-fat, high-energy diet containing moderately low (LMg, 0.116 ± 0.001 g/kg or normal (NMg, 0.516 ± 0.007 g/kg Mg for 13 weeks. The growth, body composition, mineral homeostasis, bone development, and glucose metabolism of the rats were examined. OP and OR rats showed differences (p < 0.05 in many physical and biochemical measures regardless of diet. OP and OR rats fed the LMg diet had decreased body weight, lean body mass, decreased femoral size (width, weight, and volume, and serum Mg and potassium concentrations compared to rats fed the NMg diet. The LMg diet increased serum calcium (Ca concentration in both rat strains with a concomitant decrease in serum parathyroid hormone concentration only in the OR strain. In the femur, Mg concentration was reduced, whereas concentrations of Ca and sodium were increased in both strains fed the LMg diet. Plasma glucose and insulin concentrations in an oral glucose tolerance test were similar in rats fed the LMg or NMg diets. These results show that a moderately low Mg diet impairs the growth of lean body mass and alters femoral geometry and mineral metabolism in OP and OR rats fed a high-energy diet.

Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

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Lubaczeuski, C.; Balbo, S.L.; Ribeiro, R.A.; Vettorazzi, J.F.; Santos-Silva, J.C.; Carneiro, E.M.; Bonfleur, M.L.

2015-01-01

The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca 2+ mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca 2+ mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats

Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats

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Liu, Penghao; Xie, Qihai; Wei, Tong; Chen, Yichen; Chen, Hong; Shen, Weili

2015-01-01

Objective: Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF). Methods and results: Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in both strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas. Conclusions: These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction. - Highlights: • NLRP3 is involved in obesity-induced vascular dysfunction. • Impaired mitochondrial dynamics may have been linked to mitochondrial defect and inflammasome activation. • Obesity seems to accelerate vascular dysfunction via NLRP3 activation and mitochondrial dysfunction.

Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats

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Liu, Penghao [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Xie, Qihai [Department of Cardiology, Shanghai Jiading District Central Hospital, Shanghai (China); Wei, Tong [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Chen, Yichen [Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Chen, Hong, E-mail: hchen100@shsmu.edu.cn [Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Shen, Weili, E-mail: wlshen@sibs.ac.cn [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

2015-12-04

Objective: Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF). Methods and results: Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in both strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas. Conclusions: These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction. - Highlights: • NLRP3 is involved in obesity-induced vascular dysfunction. • Impaired mitochondrial dynamics may have been linked to mitochondrial defect and inflammasome activation. • Obesity seems to accelerate vascular dysfunction via NLRP3 activation and mitochondrial dysfunction.

Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome.

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Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

2014-12-02

Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean rats). DS/obese rats fed the normal-salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The Cooccurrence of Obesity, Osteoporosis, and Sarcopenia in the Ovariectomized Rat: A Study for Modeling Osteosarcopenic Obesity in Rodents.

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Ezzat-Zadeh, Zahra; Kim, Jeong-Su; Chase, P Bryant; Arjmandi, Bahram H

2017-01-01

Obesity, osteoporosis, and sarcopenia may individually occur due to age-related gradual alterations in body composition. This study investigates the cooccurrence of these age-related diseases in female animals with low levels of ovarian hormone in the absence of complex multifactorial process of chronological aging. Thirty-six 5- and 10-month-old female rats were chosen to model pre- and postmenopausal women, respectively. Rats were divided into three treatment groups in each age category-sham, ovariectomized (ovx), and ovx + E 2 (17 β -estradiol, 10  μ g/kg)-and were pair-fed. Volunteer wheel running activity, body composition, bone microstructure, serum C-telopeptides of type I collagen, bone specific alkaline phosphatase, E 2 , and gastrocnemius and soleus muscles were analyzed. The cooccurrence of osteoporosis, sarcopenia, and obesity was observed in the older ovx rats associated with a significant ( p obesity and body composition translational research in females without the confounding effect of genetic background.

Differential Effect of Electroacupuncture on Inflammatory Adipokines in Two Rat Models of Obesity

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Jacqueline J.T. Liaw

2016-08-01

Full Text Available Chronic inflammation is known to be associated with visceral obesity and insulin resistance which are characterized by altered levels of production of pro- and anti-inflammatory adipokines. The dysregulation of the production of inflammatory adipokines and their functions in obese individuals leads to a state of chronic low-grade inflammation and may promote obesity-linked metabolic disorders and cardiovascular diseases such as insulin resistance, metabolic syndrome, and atherosclerosis. Electroacupuncture (EA was tested to see if there was a difference in its effect on pro- and anti-inflammatory adipokine levels in the blood serum and the white adipose tissue of obese Zucker fatty rats and high-fat diet-induced obese Long Evans rats. In the two rat models of obesity, on Day 12 of treatment, repeated applications of EA were seen to have had a significant differential effect for serum tumor necrosis factor-α, adiponectin, the adiponectin:leptin ratio, and blood glucose. For the adipose tissue, there was a differential effect for adiponectin that was on the borderline of significance. To explore these changes further and how they might affect insulin resistance would require a modification to the research design to use larger group sizes for the two models or to give a greater number of EA treatments.

Anti obese potential of Cucurbita maxima seeds oil: effect on lipid profile and histoarchitecture in high fat diet induced obese rats.

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Kalaivani, A; Sathibabu Uddandrao, V V; Brahmanaidu, P; Saravanan, Ganapathy; Nivedha, P R; Tamilmani, P; Swapna, K; Vadivukkarasi, Sasikumar

2017-10-19

In this study, we made an attempt to evaluate the potential of Cucurbita maxima seeds oil (CSO) against high-fat diet (HFD)-induced obesity in rats. We investigated the effect of CSO (100 mg/kg body weight) supplementation over 30 days on the changes of HFD-induced obese rats in body weight, biochemical parameters and lipid profile as well as investigated the effects of CSO on the histopathological changes. Oral administration with CSO revealed significant diminution in body weight gain, glucose and insulin levels, which altered the activity of lipid profile and restored the pathological alterations. It demonstrated that CSO had considerably altered these parameters when evaluated with HFD control rats. In conclusion, this study established that CSO prevents the HFD-induced obesity by altering the markers important to lipid metabolism.

Cardiac β-adrenergic responsiveness of obese Zucker rats: The role of AMPK.

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Bussey, Carol T; Thaung, Hp Aye; Hughes, Gillian; Bahn, Andrew; Lamberts, Regis R

2018-06-05

What is the central question of the study? What is the main finding and its importance? 1. Is the reduced signalling of AMPK, a key regulator of energy homeostasis in the heart, responsible for the reduced β-adrenergic responsiveness of the heart in obesity? 2. Inhibition of AMPK in isolated hearts prevented the reduced cardiac β-adrenergic responsiveness of obese rats, which was accompanied by reduced phosphorylation of AMPK, a proxy of AMPK activity. This suggests a direct functional link between β-adrenergic responsiveness and AMPK signalling in the heart, and that AMPK might be an important target to restore the β-adrenergic responsiveness in the heart in obesity. The obesity epidemic impacts heavily on cardiovascular health, in part due to changes in cardiac metabolism. AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis in the heart, and is regulated by β-adrenoceptors (AR) under normal conditions. In obesity, chronic sympathetic overactivation leads to impaired cardiac β-AR responsiveness, although it is unclear whether AMPK signalling, downstream of β-AR, contributes to this dysfunction. Therefore, we aimed to determine whether reduced AMPK signalling is responsible for the reduced β-AR responsiveness in obesity. In isolated hearts of lean and obese Zucker rats, we tested β-AR responsiveness to β 1 -AR agonist isoproterenol (ISO, 1 × 10 -10 - 5 × 10 -8  M) in the absence and presence of the AMPK inhibitor compound C (CC, 10 μM). β 1 -AR expression and AMPK phosphorylation were assessed by Western blot. β-Adrenergic responsiveness was reduced in the hearts of obese rats (LogEC50 of ISO-developed pressure dose-response curves: lean -8.53 ± 0.13 vs. obese -8.35 ± 0.10 10 x M; p  0.05, n = 6 per group). β 1 -AR expression and AMPK phosphorylation were reduced in hearts of obese rats (AMPK at Thr 172 : lean 1.73 ± 0.17 vs. lean CC 0.81 ± 0.13, and obese 1.18 ± 0.09 vs. obese CC 0.81 ± 0

Dietary D-psicose reduced visceral fat mass in high-fat diet-induced obese rats.

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Chung, Young-Mee; Hyun Lee, Joo; Youl Kim, Deuk; Hwang, Se-Hee; Hong, Young-Ho; Kim, Seong-Bo; Jin Lee, Song; Hye Park, Chi

2012-02-01

D-Psicose, a C-3 epimer of D-fructose, has shown promise in reducing body fat accumulation in normal rats and plasma glucose level in genetic diabetic mice. Effects of D-psicose on diet-induced obesity are not clearly elucidated, and we investigated food intake, body weight, and fat accumulation in rats fed high-fat (HF) diet. Sprague-Dawley rats became obese by feeding HF diet for 4 wk, and were assigned either to normal or HF diet supplemented with or without D-psicose, sucrose, or erythritol for 8 wk. Changing HF to normal diet gained less body weight and adipose tissue due to different energy intake. D-psicose-fed rats exhibited lower weight gain, food efficiency ratio, and fat accumulation than erythritol- and sucrose-fed rats. This effect was more prominent in D-psicose-fed rats with normal diet than with HF diet, suggesting combination of psicose and calorie restriction further reduced obesity. There was no difference in serum cholesterol/high-density lipoprotein (HDL)-C and low-density lipoprotein (LDL)-C/HDL-C ratios between D-psicose group and other groups. Liver weight in 5% psicose group with normal diet was higher than in other groups, but histopathological examination did not reveal any psicose-related change. D-Psicose inhibited the differentiation of mesenchymal stem cell (MSC) to adipose tissue in a concentration-dependent manner. These results demonstrate that D-psicose produces a marked decrease, greater than erythritol, in weight gain and visceral fat in an established obesity model by inhibiting MSC differentiation to adipocyte. Thus, D-psicose can be useful in preventing and reducing obesity as a sugar substitute and food ingredient. We can develop D-psicose as a sugar substitute and food ingredient since it can prevent obesity in normal people, but also suppress adiposity as a sugar substitute or food ingredients with antiobesity effect in obese people. D-psicose can be unique functional sweetener because of its function of reducing visceral

Adverse effects of melatonin on rat pups of Wistar-Kyoto dams receiving melatonin supplementation during pregnancy.

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Singh, Harbindar Jeet; Keah, Lee Siew; Kumar, Arun; Sirajudeen, K N S

2012-11-01

This report documents an incidental finding during a study investigating the effects of melatonin supplementation on the development of blood pressure in SHR. Administration of 10 mg/kg/day of melatonin in drinking water during pregnancy to Wistar-Kyoto (WKY) dams caused a loss of more than 50% of the pups by the age of three weeks and 95% by the age of 6 weeks. There was no maternal morbidity or mortality in the two strains or death of any of the SHR pups. No obvious physical defects were present but mean body weight was lower in the surviving WKY rats when compared to that of melatonin supplemented SHR or non-supplemented WKY pups. The reason for the high mortality in WKY pups is uncertain and appears to be strain if not batch specific. There is a need for caution in its use, particularly during pregnancy, and clearly necessitates more detailed studies. Copyright © 2011 Elsevier GmbH. All rights reserved.

L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

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Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

2009-02-01

The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

[Effects of octreotide on fatty infiltration of the pancreas in high-fat diet induced obesity rats].

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Yu, Tao; Liu, Rui; Li, Mao; Li, Xian; Qiang, Ou; Huang, Wei; Tang, Chengwei

2014-03-01

To investigate effects of octreotide on fatty infiltration of the pancreas in high-fat diet induced obesity rats. SD rats were divided into control group (n = 14) and high-fat diet group (n = 36). Obese rats from the high-fat diet group were further divided into 2 groups: the obese group (n = 14) and the octreotide-treated group (n = 16). Rats in the octreotide-treated group were subcutaneously injected with octreotide per 12 h (40 mg/kg BW) for 8 days. Body weight, fasting plasma glucose (FPG), fasting serum insulin, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) levels, pancreatic TG and FFA content were measured. Homeostatic model assessment (HOMA) index was calculated. Somatostatin (SST) and the expression of adipose differentiation-related protein (ADFP) in pancrea were measured. Pathological changes of pancreas were examined with light microscopy. Body weight, Lee's index, FPG, fasting serum insulin, TG, TC levels and HOMA index in the obese group were higher than those in the control group (P pancreas, and lowering the levels of plasma glucose and lipid in the high-fat diet induced obesity rats.

Maternal separation affects dopamine transporter function in the Spontaneously Hypertensive Rat: An in vivo electrochemical study

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Womersley Jacqueline S

2011-12-01

Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT in ways that distinguish SHR from control rat strains. Methods SHR and control Wistar-Kyoto (WKY rats were subjected to maternal separation for 3 hours per day from postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like behaviour followed by in vivo chronoamperometry to determine whether changes had occurred in striatal clearance of dopamine by DAT. The rate of disappearance of ejected dopamine was used as a measure of DAT function. Results Consistent with a model for ADHD, SHR were more active than WKY in the open field. SHR entered the inner zone more frequently and covered a significantly greater distance than WKY. Maternal separation increased the time that WKY spent in the closed arms and latency to enter the open arms of the elevated plus maze, consistent with other rat strains. Of note is that, maternal separation failed to produce anxiety-like behaviour in SHR. Analysis of the chronoamperometric data revealed that there was no difference in DAT function in the striatum of non-separated SHR and WKY. Maternal separation decreased the rate of dopamine clearance (k-1 in SHR striatum. Consistent with this observation, the dopamine clearance time (T100 was increased in SHR. These results suggest that the chronic mild stress of

Down-regulation of hypothalamic pro-opiomelanocortin (POMC) expression after weaning is associated with hyperphagia-induced obesity in JCR rats overexpressing neuropeptide Y.

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Diané, Abdoulaye; Pierce, W David; Russell, James C; Heth, C Donald; Vine, Donna F; Richard, Denis; Proctor, Spencer D

2014-03-14

We hypothesised that hypothalamic feeding-related neuropeptides are differentially expressed in obese-prone and lean-prone rats and trigger overeating-induced obesity. To test this hypothesis, in the present study, we measured energy balance and hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA expressions in male JCR:LA-cp rats. We compared, in independent cohorts, free-feeding obese-prone (Obese-FF) and lean-prone (Lean-FF) rats at pre-weaning (10 d old), weaning (21-25 d old) and early adulthood (8-12 weeks). A group of Obese-pair-feeding (PF) rats pair-fed to the Lean-FF rats was included in the adult cohort. The body weights of 10-d-old Obese-FF and Lean-FF pups were not significantly different. However, when the pups were shifted from dams' milk to solid food (weaning), the obese-prone rats exhibited more energy intake over the days than the lean-prone rats and higher body and fat pad weights and fasting plasma glucose, leptin, insulin and lipid levels. These differences were consistent with higher energy consumption and lower energy expenditure. In the young adult cohort, the differences between the Obese-FF and Lean-FF rats became more pronounced, yielding significant age effects on most of the parameters of the metabolic syndrome, which were reduced in the Obese-PF rats. The obese-prone rats displayed higher NPY expression than the lean-prone rats at pre-weaning and weaning, and the expression levels did not differ by age. In contrast, POMC expression exhibited significant age-by-genotype differences. At pre-weaning, there was no genotype difference in POMC expression, but in the weanling cohort, obese-prone pups exhibited lower POMC expression than the lean-prone rats. This genotype difference became more pronounced at adulthood. Overall, the development of hyperphagia-induced obesity in obese-prone JCR rats is related to POMC expression down-regulation in the presence of established NPY overexpression.

Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

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Lubaczeuski, C.; Balbo, S.L. [Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR (Brazil); Ribeiro, R.A. [Universidade Federal do Rio de Janeiro, Macaé, RJ (Brazil); Vettorazzi, J.F.; Santos-Silva, J.C.; Carneiro, E.M. [Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP (Brazil); Bonfleur, M.L. [Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR (Brazil)

2015-02-24

The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca{sup 2+} mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca{sup 2+} mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

Different natriuretic responses in obese and lean rats in response to nitric oxide reduction.

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Ambrozewicz, Marta A; Khraibi, Ali A; Simsek-Duran, Fatma; DeBose, Sophia C; Baydoun, Hind A; Dobrian, Anca D

2011-08-01

Nitric oxide (NO) is an important regulator of renal sodium transport and participates in the control of natriuresis and diuresis. In obesity, the nitric oxide bioavailability was reportedly reduced, which may contribute to the maintenance of hypertension. The aim of this study was to determine the effect of NO depletion on renal sodium handling in a model of diet-induced obesity hypertension. Obese hypertensive (obesity-prone (OP)) and lean normotensive (obesity-resistant (OR)) Sprague-Dawley rats were treated with 1.2 mg/kg/day N(G)-nitro-L-arginine-methyl ester (L-NAME) for 4 weeks to inhibit NO synthesis. Acute pressure natriuresis and diuresis were measured in response to an increase in perfusion pressure. NHE3 and Na(+), K(+)-ATPase protein expression were measured by Western blot and NHE3 activity was determined as the rate of pH change in brush border membrane vesicles. NHE3 membrane localization was determined by confocal microscopy. L-NAME did not significantly attenuate the natriuretic and diuretic responses to increases in renal perfusion pressure (RPP) in OP rats while inducing a significant reduction in OR rats. Following chronic NO inhibition, NHE3 protein expression and activity and Na(+), K(+)-ATPase protein expression were significantly increased in the OR but not in the OP group. Immunofluorescence studies indicated that the increase in NHE3 activity could be, at least in part, due to NHE3 membrane trafficking. Obese hypertensive rats have a weaker natriuretic response in response to NO inhibition compared to lean rats and the mechanism involves different regulation of the apical sodium exchanger NHE3 expression, activity, and trafficking.

Effect of soy protein on obesity-linked renal and pancreatic disorders in female rats

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Osman, H.F.; El-Sherbiny, E.M.

2006-01-01

The purpose of this study was to identify the effect of soy protein based diet on renal and pancreatic disorders in female obese rats. Animals assigned into group I in which 30 rats fed on a balanced diet. Group II contained 30 rats fed on a diet containing 30% fats for 4 weeks. At the end of the 4 th week, one-half of each group was treated as group III which contain 15 rats (half of group I) fed on diet containing 25% soy protein for 3 weeks and represents soy protein group, and the other half served as control. Group IV contained 15 rats (half of group II) fed on a diet containing 25% soy protein for 3 weeks and served as obese + soy protein group, and the other half fed on a normal balanced diet for 3 weeks and represents the obese group. Body weights of rats were recorded every week during the experimental period. Renal and pancreatic functions were measured as urea, creatinine, glomerular filtration rate (creatinine clearance), ammonia, sodium and potassium ions, total protein, albumin, globulin, glucose, insulin and alpha-amylase activity. Feeding with soy protein led to a very high significant increase in urea while creatinine was significantly decreased and creatinine clearance was significantly increased in the groups fed on soy protein. Ammonia concentration was increased in all groups and there was non-significant alteration in sodium and potassium ion concentrations. In soy protein groups (groups III and IV), total protein, albumin and globulin levels were increased. Glucose level was increased in obese rats and significantly decreased in groups III and IV. In group IV, insulin level was decreased which implicated to insulin excess in obesity. Soy protein decreased alpha-amylase activity in groups III and IV as compared to control rats. From these results, soy protein have a direct and protective effect on glomerular disorders and pancreatic secretions. This may be due to isoflavone contents in soy which can modulate the disturbance in metabolism

Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats.

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Wang, Jing-Hua; Kim, Bong-Soo; Han, Kyungsun; Kim, Hojun

2017-05-23

Changes in gut microbiota (GM) are closely associated with metabolic syndrome, obesity, type 2 diabetes and so on. Several medicinal herbs, including Ephedra sinica (Es), have anti-obesity effects that ameliorate metabolic disorders. Therefore, in this study we evaluated whether Es maintains its anti-obesity effect through Es-altered gut microbiota (EsM) transplantation. GM was isolated from cecal contents of Es treated and untreated rats following repeated transplants into obese rats via oral gavage over three weeks. High-fat-diet (HFD)-induced obese rats transplanted with EsM lost significant body weight, epididymal fat, and perirenal fat weight, but no remarkable changes were observed in abdominal fat, liver, cecum weight and food efficiency ratio. In addition, treatment with EsM also significantly lowered the fasting blood glucose, serum insulin level, and insulin resistance index. Meanwhile, EsM transplantation significantly reduced gene expression of proinflammatory cytokines interleukin-1 and monocyte chemotactic protein-1. Rats treated with EsM also showed changed GM composition, especially blautia, roseburia and clostridium, significantly reduced the level of endotoxin and markedly increased the acetic acid in feces. Overall, our results demonstrated that EsM ameliorates HFD-induced obesity and related metabolic disorders, like hyperglycemia and insulin resistance, and is strongly associated with modulating the distribution of GM, enterogenous endotoxin and enteral acetic acid.

Behavioral and genetic evidence for a novel animal model of Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Subtype

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Zhang-James Y

2008-12-01

Full Text Available Abstract Background According to DSM-IV there are three subtypes of Attention-Deficit/Hyperactivity Disorder, namely: ADHD predominantly inattentive type (ADHD-PI, ADHD predominantly Hyperactive-Impulsive Type (ADHD-HI, and ADHD combined type (ADHD-C. These subtypes may represent distinct neurobehavioral disorders of childhood onset with separate etiologies. The diagnosis of ADHD is behaviorally based; therefore, investigations into its possible etiologies should be based in behavior. Animal models of ADHD demonstrate construct validity when they accurately reproduce elements of the etiology, biochemistry, symptoms, and treatment of the disorder. Spontaneously hypertensive rats (SHR fulfill many of the validation criteria and compare well with clinical cases of ADHD-C. The present study describes a novel rat model of the predominantly inattentive subtype (ADHD-PI. Methods ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. Several strains with varied genetic background were needed to determine what constitutes a normal comparison. Five groups of rats were used: SHR/NCrl spontaneously hypertensive and WKY/NCrl Wistar/Kyoto rats from Charles River; SD/NTac Sprague Dawley and WH/HanTac Wistar rats from Taconic Europe; and WKY/NHsd Wistar/Kyoto rats from Harlan. DNA was analyzed to determine background differences in the strains by PCR genotyping of eight highly polymorphic microsatellite markers and 2625 single nucleotide polymorphisms (SNPs. Results Compared to appropriate comparison strains (WKY/NHsd and SD/NTac rats, SHR/NCrl showed ADHD-C-like behavior: striking overactivity and poor sustained attention. Compared to WKY/NHsd rats, WKY/NCrl rats showed inattention, but no overactivity or impulsiveness. WH/HanTac rats deviated significantly from the other control groups by being more active and less attentive than the WKY/NHsd and SD/NTac rats. We also found substantial

Obesity and the use of antibiotics and probiotics in rats.

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de Sá Del Fiol, Fernando; Tardelli Ferreira, Alessandra Cristina Marciano; Marciano, Jorge José; Marques, Maria Claudia; Sant'Ana, Luciane Lopes

2014-01-01

Obesity has become a major public health challenge in recent years. Recent studies suggest that alterations of the gut microbiota by antibiotics could play an important role in obesity. We investigated this topic using 60 Wistar rats, which were divided into 3 experimental groups: rats treated with amoxicillin, rats treated with amoxicillin plus Saccharomyces boulardii and controls. Treatments were administered over the course of 2 weeks. Tetrapolar bioelectric impedance analysis and anthropometric evaluations were conducted. The body mass index was significantly lower for the animals in the control group (p = 0.034). The same result was observed for the Lee index: the control group had a lower index than the 2 groups that received antibiotic treatment (p = 0.0019). The total body water data demonstrated that the control group had the greatest amount of body water (279.1 g, p = 0.0243). The groups treated with the antibiotic exhibited a greater accumulation of body fat than the control group.

Differential Responses to Blood Pressure and Oxidative Stress in Streptozotocin-Induced Diabetic Wistar-Kyoto Rats and Spontaneously Hypertensive Rats: Effects of Antioxidant (Honey) Treatment

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Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd Suhaimi Ab; Sirajudeen, Kuttulebbai N. S.; Salleh, Md Salzihan Md; Gurtu, Sunil

2011-01-01

Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress. PMID:21673929

Modulation of olfactory sensitivity and glucose sensing by the feeding state in obese Zucker rats.

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Pascaline eAimé

2014-09-01

Full Text Available The Zucker fa/fa rat has been widely used as an animal model to study obesity, since it recapitulates most of its behavioral and metabolic dysfunctions, such as hyperphagia, hyperglycemia and insulin resistance. Although it is well established that olfaction is under nutritional and hormonal influences, little is known about the impact of metabolic dysfunctions on olfactory performances and glucose-sensing in the olfactory system of the obese Zucker rat. In the present study, using a behavioral paradigm based on a conditioned olfactory aversion, we have shown that both obese and lean Zucker rats have a better olfactory sensitivity when they are fasted than when they are satiated. Interestingly, the obese Zucker rats displayed a higher olfactory sensitivity than their lean controls. By investigating the molecular mechanisms involved in glucose-sensing in the olfactory system, we demonstrated that sodium-coupled glucose transporters 1 (SGLT1 and insulin dependent glucose transporters 4 (GLUT4 are both expressed in the olfactory bulb (OB. By comparing the expression of GLUT4 and SGLT1 in OB of obese and lean Zucker rats, we found that only SGLT1 is regulated in genotype-dependent manner. Next, we used glucose oxidase biosensors to simultaneously measure in vivo the extracellular fluid glucose concentrations ([Gluc]ECF in the OB and the cortex. Under metabolic steady state, we have determined that the OB contained twice the amount of glucose found in the cortex. In both regions, the [Gluc]ECF was 2 fold higher in obese rats compared to their lean controls. Under induced dynamic glycemia conditions, insulin injection produced a greater decrease of [Gluc]ECF in the OB than in the cortex. Glucose injection did not affect OB [Gluc]ECF in Zucker fa/fa rats. In conclusion, these results emphasize the importance of glucose for the OB network function and provide strong arguments towards establishing the OB glucose-sensing as a key factor for sensory

Targeted delivery using peptide-functionalised gold nanoparticles to white adipose tissues of obese rats

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Thovhogi, Ntevheleni; Sibuyi, Nicole [Medical Research Council, Diabetes Research Group (South Africa); Meyer, Mervin [University of the Western Cape, Biotechnology Department, DST/Mintek Nanotechnology Innovation Centre (South Africa); Onani, Martin [University of the Western Cape, Chemistry Department (South Africa); Madiehe, Abram, E-mail: amadiehe@csir.co.za [Medical Research Council, Diabetes Research Group (South Africa)

2015-02-15

Obesity is a complex metabolic disease of excessive fat accumulation. It is a worldwide epidemic affecting billions of people. Current pharmacological treatment of obesity remains limited and ineffective due to systemic drug toxicity and undesirable side effects. The current epidemic raises a serious need for development of safer drugs to treat obesity. Nanotechnology-based drug delivery system for administering pharmaceutical compound to achieve therapeutic effects is currently an exciting field in cancer treatment. Drug delivery involves either modification of drug release profile, absorption, distribution and/or elimination, for the benefit of improving drug efficacy and safety. Therefore, nanotechnology holds promise in the treatment of diseases including obesity. Gold nanoparticles (GNPs) functionalised with different biomolecules have been successfully used as drug delivery, labelling and imaging tools in biomedical research. In this study, the binding-specificity and targeting ability of adipose homing peptide (AHP)-functionalised GNPs (AHP-GNPs) were evaluated using flow cytometry and inductively coupled plasma-optical emission spectroscopy. Caco-2 cells and rats fed either chow or a high-fat diet were treated with either unfunctionalised GNPs or AHP-GNPs. Cellular uptake of GNPs was detected in cells treated with AHP-GNPs and not those treated with GNPs alone. Binding of AHP to cells was both temperature- and concentration-dependent. Compared to rats treated with GNPs alone, treatment of obese rats with AHP-GNPs resulted in the targeted delivery of the GNPs to the white adipose tissue (WAT). This paper reports the successful targeting of AHP-functionalised GNPs to WAT of obese rats.

Targeted delivery using peptide-functionalised gold nanoparticles to white adipose tissues of obese rats

International Nuclear Information System (INIS)

Thovhogi, Ntevheleni; Sibuyi, Nicole; Meyer, Mervin; Onani, Martin; Madiehe, Abram

2015-01-01

Obesity is a complex metabolic disease of excessive fat accumulation. It is a worldwide epidemic affecting billions of people. Current pharmacological treatment of obesity remains limited and ineffective due to systemic drug toxicity and undesirable side effects. The current epidemic raises a serious need for development of safer drugs to treat obesity. Nanotechnology-based drug delivery system for administering pharmaceutical compound to achieve therapeutic effects is currently an exciting field in cancer treatment. Drug delivery involves either modification of drug release profile, absorption, distribution and/or elimination, for the benefit of improving drug efficacy and safety. Therefore, nanotechnology holds promise in the treatment of diseases including obesity. Gold nanoparticles (GNPs) functionalised with different biomolecules have been successfully used as drug delivery, labelling and imaging tools in biomedical research. In this study, the binding-specificity and targeting ability of adipose homing peptide (AHP)-functionalised GNPs (AHP-GNPs) were evaluated using flow cytometry and inductively coupled plasma-optical emission spectroscopy. Caco-2 cells and rats fed either chow or a high-fat diet were treated with either unfunctionalised GNPs or AHP-GNPs. Cellular uptake of GNPs was detected in cells treated with AHP-GNPs and not those treated with GNPs alone. Binding of AHP to cells was both temperature- and concentration-dependent. Compared to rats treated with GNPs alone, treatment of obese rats with AHP-GNPs resulted in the targeted delivery of the GNPs to the white adipose tissue (WAT). This paper reports the successful targeting of AHP-functionalised GNPs to WAT of obese rats

Targeted delivery using peptide-functionalised gold nanoparticles to white adipose tissues of obese rats

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Thovhogi, Ntevheleni; Sibuyi, Nicole; Meyer, Mervin; Onani, Martin; Madiehe, Abram

2015-02-01

Obesity is a complex metabolic disease of excessive fat accumulation. It is a worldwide epidemic affecting billions of people. Current pharmacological treatment of obesity remains limited and ineffective due to systemic drug toxicity and undesirable side effects. The current epidemic raises a serious need for development of safer drugs to treat obesity. Nanotechnology-based drug delivery system for administering pharmaceutical compound to achieve therapeutic effects is currently an exciting field in cancer treatment. Drug delivery involves either modification of drug release profile, absorption, distribution and/or elimination, for the benefit of improving drug efficacy and safety. Therefore, nanotechnology holds promise in the treatment of diseases including obesity. Gold nanoparticles (GNPs) functionalised with different biomolecules have been successfully used as drug delivery, labelling and imaging tools in biomedical research. In this study, the binding-specificity and targeting ability of adipose homing peptide (AHP)-functionalised GNPs (AHP-GNPs) were evaluated using flow cytometry and inductively coupled plasma-optical emission spectroscopy. Caco-2 cells and rats fed either chow or a high-fat diet were treated with either unfunctionalised GNPs or AHP-GNPs. Cellular uptake of GNPs was detected in cells treated with AHP-GNPs and not those treated with GNPs alone. Binding of AHP to cells was both temperature- and concentration-dependent. Compared to rats treated with GNPs alone, treatment of obese rats with AHP-GNPs resulted in the targeted delivery of the GNPs to the white adipose tissue (WAT). This paper reports the successful targeting of AHP-functionalised GNPs to WAT of obese rats.

Increased risk of cataract development in WNIN-obese rats due to accumulation of intralenticular sorbitol.

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Reddy, Paduru Yadagiri; Giridharan, Nappan Veettil; Balakrishna, Nagalla; Validandi, Vakdevi; Pullakhandam, Raghu; Reddy, Geereddy Bhanuprakash

2013-05-01

Epidemiological studies have reported an association between obesity and increased incidence of ocular complications including cataract, yet the underlying biochemical and molecular mechanisms remained unclear. Previously we had demonstrated accumulation of sorbitol in the lens of obese rats (WNIN/Ob) and more so in a related strain with impaired glucose tolerance (WNIN/GR-Ob). However, only a few (15-20%) WNIN/Ob and WNIN/GR-Ob rats develop cataracts spontaneously with age. To gain further insights, we investigated the susceptibility of eye lens proteins of these obese rat strains to heat- and UV-induced aggregation in vitro, lens opacification upon glucose-mediated sorbitol accumulation ex vivo, and onset and progression of cataract was followed by galactose feeding and streptozotocin (STZ) injection. The results indicated increased susceptibility toward heat- or UV-induced aggregation of lens proteins in obese animals compared to their littermate lean controls. Further, in organ culture studies glucose-induced sorbitol accumulation was found to be higher and thus the lens opacification was faster in obese animals compared to their lean littermates. Also, the onset and progression of galactose- or STZ-induced cataractogenesis was faster in obese animals compared to lean control. These results together with our previous observations suggest that obesity status could lead to hyperaccumulation of sorbitol in eye lens, predisposing them to cataract, primarily by increasing their susceptibility to environmental and/or physiological factors. Further, intralenticular sorbitol accumulation beyond a threshold level could lead to cataract in WNIN/Ob and WNIN/GR-Ob rats. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Lipogenesis from U14C lactate in obese Zucker rat hepatocytes. Effect of albumin-bound oleate

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Porquet, D.; Serbource-Goguel, N.; Durand, G.; Maccario, J.; Feger, J.; Agneray, J.

1984-01-01

Lipogenesis from U( 14 C) lactate was studied in hepatocytes isolated from obese Zucker rats (fa/fa) their lean littermates (Fa/.) and Sprague Dawley rats. The distribution of radioactive carbon between the glycerol and the fatty acid moieties of the acylglycerols were studied. Radioactive lactate was better utilized for glycerol formation than it was for fatty acid formation in the obese rats. However, when oleate was added to the hepatocytic incubation medium, radioactive lactate was preferentially incorporated into the fatty acid moiety of the acyglycerols. Among the nutrients, lactate seems to be a better source of carbon than glucose for lipid synthesis. It has been shown that there is increased hepatic portal blood concentration of lactate several hours after eating: about 4 mM in Wistar rats and 10-15 mM in obese Zucher rats. We are interested in determin the incorporation of carbon from lactate either into glycerol or into fatty acid moieties of hepatic acylgylcerols, and in determining the influence of exogenous fatty acids on acylgylcerol synthesis, since a high level of circulating fatty acids in Zucher obese rats has been reported. The purpose was to determine the incorporaton of lactate into glycerol and fatty moieties of acylglycerols, under the influence of oleate

A COMBINED EFFECT OF DEXTROMETHORPHAN AND MELATONIN ON NEUROPATHIC PAIN BEHAVIOR IN RATS

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Wang, Shuxing; Zhang, Lin; Lim, Grewo; Sung, Backil; Tian, Yinghong; Chou, Chiu-Wen; Hernstadt, Hayley; Rusanescu, Gabriel; Ma, Yuxin; Mao, Jianren

2009-01-01

Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-D-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain. PMID:19595681

Diet composition alters the satiety effect of cholecystokinin in lean and obese Zucker rats.

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Maggio, C A; Haraczkiewicz, E; Vasselli, J R

1988-01-01

Although exogenous administration of the peptide cholecystokinin (CCK) has been shown to reduce food intake in a variety of experimental situations, few studies have examined the influence of dietary content upon CCK's effectiveness, particularly in obese states. To evaluate the effectiveness of CCK administration in animals consuming high fat diets, groups of obese and lean Zucker rats were maintained on laboratory chow (CH), a high fat diet isocaloric to chow (IF), or a hypercaloric fat diet (HF). After a 17 hr fast, rats were given intraperitoneal injections of saline or ascending doses of 0.06 to 2.0 micrograms/kg of the synthetic octapeptide of CCK. On all diets, obese rats required higher doses of CCK to significantly reduce feeding and showed smaller intake reductions than lean rats (p less than 0.001). Despite higher baseline caloric intakes (p less than 0.001), rats of both genotypes maintained on HF displayed larger reductions of intake than those fed IF or CH (p less than 0.001). Intake reductions by either genotype maintained on IF or CH were not reliably different. The manner in which the satiety effect of CCK was enhanced in rats consuming the calorically dense, palatable HF diet is unclear but may be related to orosensory and/or postingestive attributes of the diet.

Sensory-specific satiety is intact in rats made obese on a high-fat high-sugar choice diet.

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Myers, Kevin P

2017-05-01

Sensory-specific satiety (SSS) is the temporary decreased pleasantness of a recently eaten food, which inhibits further eating. Evidence is currently mixed whether SSS is weaker in obese people, and whether such difference precedes or follows from the obese state. Animal models allow testing whether diet-induced obesity causes SSS impairment. Female rats (n = 24) were randomly assigned to an obesogenic high-fat, high-sugar choice diet or chow-only control. Tests of SSS involved pre-feeding a single palatable, distinctively-flavored food (cheese- or cocoa-flavored) prior to free choice between both foods. Rats were tested for short-term SSS (2 h pre-feeding immediately followed by 2 h choice) and long-term SSS (3 day pre-feeding prior to choice on day 4). In both short- and long-term tests rats exhibited SSS by shifting preference towards the food not recently eaten. SSS was not impaired in obese rats. On the contrary, in the long-term tests they showed stronger SSS than controls. This demonstrates that neither the obese state nor a history of excess energy consumption fundamentally causes impaired SSS in rats. The putative impaired SSS in obese people may instead reflect a specific predisposition, properties of the obesogenic diet, or history of restrictive dieting and bingeing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulatory effects of dietary supplementation by Vernonia amygdalina on high-fat-diet-induced obesity in Wistar rats.

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Ekeleme-Egedigwe, Chima A; Ijeh, Ifeoma I; Okafor, Polycarp N

2017-01-01

Obesity is a growing public health problem arising from energy imbalance. The effect of 10% dietary incorporation of Vernonia amygdalina (VA) leaves into high-fat diets on some biological markers of adiposity and dyslipidaemia was investigated. Experimental diets consisted of the following – CD (control diet); HFD (high-fat diet); and HFD- VA (HFD containing 10% Vernonia amygdalina leaves) supplementation. Fifteen male Wistar rats were randomly divided into three groups of five animals each. After twelve weeks of feeding, serum lipid profile, blood glucose concentrations, body weight, adiposity index, feed intake, fecal loss and relative organ weight were investigated. Vernonia amygdalina (VA) inhibited HFD-induced weight gain and adiposity in rats. HFD-induced obese rats showed a significant increase in the levels of serum TG and TC compared to rats on a normal diet. However, the levels of serum TG, TC, LDL-C in HFDVA rats reduced significantly relative to the levels in HFD rats. Our results indicate that HFDVA reversed fatty infiltration leading to decreased body weight and fat tissue mass in the rats. These results suggested that incorporation of Vernonia amygdalina into high-fat diets may have therapeutic potentials for obesity and related metabolic disorders. Further studies to explore its possibility as an alternative pharmacologic agent to treat obesity are warranted.

Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats.

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Bagi, Cedo M; Edwards, Kristin; Berryman, Edwin

2017-12-01

Metabolic syndrome and osteoporosis share similar risk factors. Also, patients with diabetes have a higher risk of osteoporosis and fracture. Liver manifestations, such as non-alcoholic steatohepatitis (NASH), of metabolic syndrome are further aggravated in diabetics and often lead to liver failure. Our objective was to create a rat model of human metabolic syndrome and determine the long-term impact of early-onset T1D on bone structure and strength in obese growing rats. Male rats were given either standard chow and RO water (Controls) or a high-fat, high-cholesterol diet and sugar water containing 55% fructose and 45% glucose (HFD). A third group of rats received the HFD diet and a single dose of streptozotocin to induce type 1 diabetes (HFD/Sz). Body weight and glucose tolerance tests were conducted several times during the course of the study. Serum chemistry, liver enzymes, and biomarkers of bone metabolism were evaluated at 10 and 28 weeks. Shear wave elastography and histology were used to assess liver fibrosis. Cancellous bone structure and cortical bone geometry were evaluated by mCT and strength by the 3-point bending method. Body mass and fat accumulation was significantly higher in HFD and HFD/Sz rats compared to Controls. Rats in both the HFD and HFD/Sz groups developed NASH, although the change was more severe in diabetic rats. Although both groups of obese rats had larger bones, their cancellous structure and cortical thickness were reduced, resulting in diminished strength that was further aggravated by diabetes. The HFD and HFD/Sz rats recapitulate MeSy in humans with liver pathology consistent with NASH. Our data provide strong indication that obesity accompanied by type 1 diabetes significantly aggravates comorbidities of MeSy, including the development of osteopenia and weaker bones. The juvenile rat skeleton seems to be more vulnerable to damage imposed by obesity and diabetes and may offer a model to inform the underlying pathology associated

Effects of intestinal bypass surgery on appetite, food intake, and body weight in obese and lean rats.

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Sclafani, A; Koopmans, H S; Vasselli, J R; Reichman, M

1978-04-01

Jejunoileal bypass surgery or sham surgery was performed in female rats made obese with ventromedial hypothalamic (VMH) knife cuts, and in lean control rats. After bypass surgery, the VMH rats underate and lost weight until they reached the body weight of the control sham rats, and they then maintained their weight at control levels. Bypass surgery in lean rats produced much smaller reductions in food intake and body weight. Both bypass groups initially consumed less of a sucrose solution and milk diet during 1 h/day tests, but their intakes returned to near normal levels during the second postoperative month. Reconnection of the intestinal tract in the VMH-bypass rats led to renewed hyperphagia and return to obese body weights. A second experiment revealed that bypass surgery reduces food intake and body weight in genetically obese (fatty) rats, but this effect is not as pronounced as that displayed by VMH rats. These results confirm recent clinical observations that reduced appetite and caloric intake are the major causes of the weight loss produced by intestinal bypass surgery.

Cardiac remodeling and myocardial dysfunction in obese spontaneously hypertensive rats

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Linz Dominik

2012-09-01

Full Text Available Abstract Background The additive effects of obesity and metabolic syndrome on left ventricular (LV maladaptive remodeling and function in hypertension are not characterized. Methods We compared an obese spontaneously hypertensive rat model (SHR-ob with lean spontaneously hypertensive rats (SHR-lean and normotensive controls (Ctr. LV-function was investigated by cardiac magnetic resonance imaging and invasive LV-pressure measurements. LV-interstitial fibrosis was quantified and protein levels of phospholamban (PLB, Serca2a and glucose transporters (GLUT1 and GLUT4 were determined by immunohistochemistry. Results Systolic blood pressure was similar in SHR-lean and SHR-ob (252 ± 7 vs. 242 ± 7 mmHg, p = 0.398 but was higher when compared to Ctr (155 ± 2 mmHg, p  Conclusion In addition to hypertension alone, metabolic syndrome and obesity adds to the myocardial phenotype by aggravating diastolic dysfunction and a progression towards systolic dysfunction. SHR-ob may be a useful model to develop new interventional and pharmacological treatment strategies for hypertensive heart disease and metabolic disorders.

Obesity and Subsequent Cardiovascular Events in Rats and The Potential Benefits of some Antioxidants Supplementation

International Nuclear Information System (INIS)

HEIBASHY, M.I.; El-Negmy, F.A.; Shahin, M.I.; Kelada, N.A.

2011-01-01

This study focuses on the relationship between the obesity and cardiovascular diseases (CVD) and the possible amelioration effects of curcumin or L-carnitine and their mixture on cardiac and lipid profiles tests. Obesity is associated with abnormal endothelial function and it is often inferred that the reduction in endothelial function is the result of a decrease in nitric oxide (NO). Moreover, asymmetric dimethyl arginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase (NOs) activity. This modified amino acid is derived from proteins that have been post-translationally methylated and subsequently hydrolyzed. In the current study, obesity was induced in the rats by receiving orally 200 mg cholesterol/100 g by the aid of gastric tube together with injection i.m. 30 mg cholic acid/100 g for one month. After one month of induction of hyper-cholesterolemia in rats and in comparison to normal rats, the results showed that incorporation of extra cholesterol in diet led to a significant increase in serum cholesterol, triglycerides, LDL, HDL, VLDL-cholesterol and resistin levels. Moreover, significant elevations in the levels of AST, LDH, CK, ADMA and endotheline-1 were recorded in obese rats compared with normal rats. All previous parameters were corrected after the hypercholesterolemic rats were treated with curcumin or L-carnitine and their mixture depending on the time of treatment. These findings are consistent with the concept that curcumin and L-carnitine are hypolipidemic agents and powerful antioxidants

Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats.

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Johnson, Paul M; Kenny, Paul J

2010-05-01

We found that development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs. Moreover, lentivirus-mediated knockdown of striatal D2Rs rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.

Exercise training starting at weaning age preserves cardiac pacemaker function in adulthood of diet-induced obese rats.

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Carvalho de Lima, Daniel; Guimarães, Juliana Bohnen; Rodovalho, Gisele Vieira; Silveira, Simonton Andrade; Haibara, Andrea Siqueira; Coimbra, Cândido Celso

2014-08-01

Peripheral sympathetic overdrive in young obese subjects contributes to further aggravation of insulin resistance, diabetes, and hypertension, thus inducing worsening clinical conditions in adulthood. Exercise training has been considered a strategy to repair obesity autonomic dysfunction, thereby reducing the cardiometabolic risk. Therefore, the aim of this study was to assess the effect of early exercise training, starting immediately after weaning, on cardiac autonomic control in diet-induced obese rats. Male Wistar rats (weaning) were divided into four groups: (i) a control group (n = 6); (ii) an exercise-trained control group (n = 6); (iii) a diet-induced obesity group (n = 6); and (iv) an exercise-trained diet-induced obesity group (n = 6). The development of obesity was induced by 9 weeks of palatable diet intake, and the training program was implemented in a motor-driven treadmill (5 times per week) during the same period. After this period, animals were submitted to vein and artery catheter implantation to assess cardiac autonomic balance by methylatropine (3 mg/kg) and propranolol (4 mg/kg) administration. Exercise training increased running performance in both groups (p Exercise training also prevented the increased resting heart rate in obese rats, which seemed to be related to cardiac pacemaker activity preservation (p exercise program beginning at weaning age prevents cardiovascular dysfunction in obese rats, indicating that exercise training may be used as a nonpharmacological therapeutic strategy for the treatment of cardiometabolic diseases.

Anti-Obesity Effects of Onion Extract in Zucker Diabetic Fatty Rats

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Kiharu Igarashi

2012-10-01

Full Text Available Anti-obesity effects of onion extract were determined in obesity and diabetes-prone Zucker diabetic fatty rats by measuring the efficacy of markers concerned with diabetes and obesity. Body and adipose tissue weights in 5% of onion extract-fed group were found to be significantly lower than the control group without onion extract. Fasting blood glucose and HOMA-IR levels were also improved, although the serum insulin and leptin levels did not show any remarkable difference. Serum triglyceride and free fatty acid levels in both the 3% and 5%-fed group were found to be reduced compared to the control group. Additionally the feeding of the onion extract increased the glucose tolerance. These results suggest that dietary onion extract is beneficial for improving diabetes by decreasing lipid levels. We also examined differentiation ability of rat white preadipocyte cells using the onion extract and its sulfur-containing components. Cycloalliin, S-methyl-l-cysteine, S-propyl-l-cysteine sulfoxide, dimethyl trisulfide, especially S-methyl-l-cysteine sulfoxide were reported to be effective in inhibiting formation of oil drop in the cells, suggesting that these compounds may be involved in the anti-obesity effect of the onion extract.

Effects of clenbuterol on insulin resistance in conscious obese Zucker rats.

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Pan, S J; Hancock, J; Ding, Z; Fogt, D; Lee, M; Ivy, J L

2001-04-01

The present study was conducted to determine the effect of chronic administration of the long-acting beta(2)-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats (fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin. kg(-1). min(-1)) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

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Akhtar, Muhammad Tayyab; Bin Mohd Sarib, Mohamad Syakir; Ismail, Intan Safinar; Abas, Faridah; Ismail, Amin; Lajis, Nordin Hj; Shaari, Khozirah

2016-08-09

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

The CD147/MMP-2 signaling pathway may regulate early stage cardiac remodelling in spontaneously hypertensive rats.

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Li, Bowei; Zhou, Wanxing; Yang, Xiaorong; Zhou, Yuliang; Tan, Yongjing; Yuan, Congcong; Song, Yulan; Chen, Xiao; Zhang, Wei

2016-11-01

Previous studies have reported that decreased matrix metalloproteinase-2 (MMP-2) is associated with early stage (age 8-16 weeks) ventricular remodelling in spontaneously hypertensive rats (SHR). We hypothesized that inhibited CD147/MMP-2 signalling might down-regulate MMP-2 expression and augment remodelling in spontaneously hypertensive rats. Twenty-nine male SHR (8 weeks) were randomly assigned to SHR, CD147, and CD147+DOX groups. The control group included eight age-matched WKY rats. CD147 and CD147+DOX groups received recombinant human CD147 (600 ng/kg in 1.5 mL saline, weekly). The SHR and WKY groups received the vehicle. The CD147+DOX group also received doxycycline, an inhibitor of MMPs (daily, 30 mg/kg in 1.5 mL saline, iG). On day 56 echocardiography and left ventricular mass index (LVWI) measurements were collected and histological sections were stained for cell and collagen content. Myocardium MMP-2, TIMP-1, CD147, and collagens types I and III were estimated by western blot. CD147 and the ratio of MMP-2/TIMP-1 were lower in SHR than WKY rats (PCD147 rats showed CD147, MMP-2 and MMP-2/TIMP-1 were increased (PCD147 levels did not differ between CD147+DOX and CD147 groups, CVF, collagens type I and III and partial fiber breaks were more abundant in CD147+DOX (PCD147/MMP-2 pathway was associated with early stage cardiac remodelling, and CD147 supplementation may attenuate this response. © 2016 John Wiley & Sons Australia, Ltd.

Preconception Prebiotic and Sitagliptin Treatment in Obese Rats Affects Pregnancy Outcomes and Offspring Microbiota, Adiposity, and Glycemia

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Carol A. Dennison

2017-10-01

Full Text Available Maternal obesity is associated with increased risk of pregnancy complications and greater risk of obesity in offspring, but studies designed to examine preconception weight loss are limited. The objective of this study was to determine if a combined dietary [oligofructose (OFS] and pharmacological (sitagliptin preconception intervention could mitigate poor pregnancy outcomes associated with maternal obesity and improve offspring metabolic health and gut microbiota composition. Diet-induced obese female Sprague-Dawley rats were randomized to one of four intervention groups for 8 weeks: (1 Obese-Control (consumed control diet during intervention; (2 Obese-OFS (10% OFS diet; (3 Obese-S (sitagliptin drug; (4 Obese-OFS + S (combination treatment. Two reference groups were also included: (5 Obese-HFS (untreated obese consumed high fat/sucrose diet throughout study; (6 Lean-Control (lean reference group that were never obese and consumed control diet throughout. Offspring consumed control diet until 11 weeks of age followed by HFS diet until 17 weeks of age. The Obese-OFS + S rats lost weight during the intervention phase whereas the OFS and S treatments attenuated weight gain compared with Obese-HFS (p < 0.05. Gestational weight gain was lowest in Obese-OFS + S rats and highest in Obese-HFS rats (p < 0.05. Prepregnancy intervention did not affect reproductive parameters but did affect pregnancy outcomes including litter size. Male Obese-OFS offspring had significantly lower percent body fat than Obese-HFS at 17 weeks. Female Obese-S and Obese-OFS offspring had significantly lower fasting glucose at 17 weeks compared with Obese-Control and Obese-HFS. Clostridium cluster XI was higher in Obese-HFS and Obese-S dams at birth compared with all other groups. Dams with an adverse pregnancy outcome had significantly lower (p = 0.035 Lactobacillus spp. compared with dams with normal or small litters. At weaning, male offspring

Decreased expression of CD36 in circumvallate taste buds of high-fat diet induced obese rats.

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Zhang, Xiao-Juan; Zhou, Li-Hong; Ban, Xiang; Liu, Dian-Xin; Jiang, Wei; Liu, Xiao-Min

2011-10-01

Mammals spontaneously prefer lipid rich foods. Overconsumption of high-fat diet leads to obesity and related diseases. Recent findings indicate that taste may participate in the orosensory perception of dietary lipids and the fatty taste may contribute to a preference for and excessive consumption of dietary fat. CD36, a trans-membrane glycoprotein, which is located in the taste buds of circumvallate papillae of rodents, appears to be a plausible receptor for this fatty taste. Obese subjects present a stronger preference for fatty foods, though the mechanisms involved are complex and are not fully investigated. Our data from immunofluorescence and real-time RT-PCR showed that the expression levels of CD36 in circumvallate taste buds were significantly lower in high-fat diet induced obese rats as compared with that of control rats fed a normal diet. These results suggest that decreased expression of CD36 in circumvallate taste buds of high-fat diet induced obese rats may be associated with diminished fatty taste sensitivity and in order to compensate the preference for dietary fat, rats consume more fatty foods. Therapeutic strategies designed to alter or manipulate CD36 expression or function in taste buds may have important implications in treating obesity and related diseases. Copyright © 2010 Elsevier GmbH. All rights reserved.

Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol.

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Toyoda, Takeshi; Cho, Young-Man; Akagi, Jun-Ichi; Mizuta, Yasuko; Matsushita, Kohei; Nishikawa, Akiyoshi; Imaida, Katsumi; Ogawa, Kumiko

2017-01-01

3-Monochloropropane-1,2-diol (3-MCPD) is a heat-induced food contaminant that has been shown to be a nongenotoxic renal carcinogen. Although the toxicity of 3-MCPD has been widely investigated for decades, there is a further concern that 3-MCPD might exert more potent toxicity in high-risk population with underlying diseases such as hyperlipidemia associated with obesity. In the present study, we performed a 13-week subchronic toxicity study for 3-MCPD using an obesity rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 9, 28.5, 90, 285, or 900 ppm 3-MCPD in drinking water for 13 weeks. 3-MCPD treatment decreased body weight gain, increased relative kidney weights, induced anemia, and induced epithelial cell necrosis in epididymal ducts in all 3 strains. The degrees of epididymal damage were higher in F344 and lean rats than in fatty rats, while renal toxicity was most potent in F344 rats and comparable in lean and fatty rats. In contrast, the hematology data indicated that anemia was worse in fatty rats than in F344 and lean rats, and a significant decrease in hematopoietic cells in the bone marrow was observed only in fatty rats. The no-observed-adverse-effect level was estimated to be 28.5 ppm in all 3 strains for 3-MCPD. These results suggested that obese Zucker rats may be more susceptible to 3-MCPD-dependent toxicity in the hematopoietic tissues than their lean counterparts.

Pepsin Egg White Hydrolysate Ameliorates Obesity-Related Oxidative Stress, Inflammation and Steatosis in Zucker Fatty Rats.

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M Garcés-Rimón

Full Text Available The aim of this work was to evaluate the effect of the administration of egg white hydrolysates on obesity-related disorders, with a focus on lipid metabolism, inflammation and oxidative stress, in Zucker fatty rats. Obese Zucker rats received water, pepsin egg white hydrolysate (750 mg/kg/day or Rhizopus aminopeptidase egg white hydrolysate (750 mg/kg/day for 12 weeks. Lean Zucker rats received water. Body weight, solid and liquid intakes were weekly measured. At the end of the study, urine, faeces, different organs and blood samples were collected. The consumption of egg white hydrolysed with pepsin significantly decreased the epididymal adipose tissue, improved hepatic steatosis, and lowered plasmatic concentration of free fatty acids in the obese animals. It also decreased plasma levels of tumor necrosis factor-alpha and reduced oxidative stress. Pepsin egg white hydrolysate could be used as a tool to improve obesity-related complications.

Increased Hypothalamic Inflammation Associated with the Susceptibility to Obesity in Rats Exposed to High-Fat Diet

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Xiaoke Wang

2012-01-01

Full Text Available Inflammation has been implicated in the hypothalamic leptin and insulin resistance resulting defective food intake during high fat diet period. To investigate hypothalamic inflammation in dietary induced obesity (DIO and obesity resistant (DIO-R rats, we established rat models of DIO and DIO-R by feeding high fat diet for 10 weeks. Then we switched half of DIO and DIO-R rats to chow food and the other half to high fat diet for the following 8 weeks to explore hypothalamic inflammation response to the low fat diet intervention. Body weight, caloric intake, HOMA-IR, as well as the mRNA expression of hypothalamic TLR4, NF-κB, TNF-α, IL-1β, and IL-6 in DIO/HF rats were significantly increased compared to DIO-R/HF and CF rats, whereas IL-10 mRNA expression was lower in both DIO/HF and DIO-R/HF rats compared with CF rats. Switching to chow food from high fat diet reduced the body weight and improved insulin sensitivity but not affecting the expressions of studied inflammatory genes in DIO rats. Take together, upregulated hypothalamic inflammation may contribute to the overeating and development of obesity susceptibility induced by high fat diet. Switching to chow food had limited role in correcting hypothalamic inflammation in DIO rats during the intervention period.

Centrally administered urocortin 2 decreases gorging on high-fat diet in in both diet induced obesity-prone and -resistant rats

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Cottone, Pietro; Sabino, Valentina; Nagy, Tim R.; Coscina, Donald V.; Levin, Barry E.; Zorrilla, Eric P.

2013-01-01

Objective Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to play a role in obesity risk. The present study tested the hypothesis that i) the microstructure of chronic high-fat diet intake differs between genetically selected Diet-Induced Obesity (DIO) and Diet Resistant (DR) rats, and ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 (CRF2) agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats. Design Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 µg). Results Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 µg, suppressing high-fat diet intake by ~40% at the 3 µg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with 2/3rd less water. Conclusions Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically-prone DIO rats, which otherwise show a “gorging” meal pattern. These results open new opportunities of investigation towards treating some forms of diet-induced obesity. PMID:23478425

The Cooccurrence of Obesity, Osteoporosis, and Sarcopenia in the Ovariectomized Rat: A Study for Modeling Osteosarcopenic Obesity in Rodents

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Zahra Ezzat-Zadeh

2017-01-01

Full Text Available Background. Obesity, osteoporosis, and sarcopenia may individually occur due to age-related gradual alterations in body composition. This study investigates the cooccurrence of these age-related diseases in female animals with low levels of ovarian hormone in the absence of complex multifactorial process of chronological aging. Methods. Thirty-six 5- and 10-month-old female rats were chosen to model pre- and postmenopausal women, respectively. Rats were divided into three treatment groups in each age category—sham, ovariectomized (ovx, and ovx + E2 (17β-estradiol, 10 μg/kg—and were pair-fed. Volunteer wheel running activity, body composition, bone microstructure, serum C-telopeptides of type I collagen, bone specific alkaline phosphatase, E2, and gastrocnemius and soleus muscles were analyzed. Results. The cooccurrence of osteoporosis, sarcopenia, and obesity was observed in the older ovx rats associated with a significant (p<0.05 increased fat mass (30%, bone loss (9.6%, decreased normalized muscle mass-to-body-weight ratio (10.5%, and a significant decrease in physical activity (57%. The ratio of tibial bone mineral density to combined muscle mass was significantly decreased in both ovx age categories. Conclusion. Ovariectomized rat could be used as an experimental model to examine the effect of loss of ovarian hormones, while controlling for energy intake and expenditure, to conduct obesity and body composition translational research in females without the confounding effect of genetic background.

Impact of metformin treatment and swimming exercise on visfatin levels in high-fat-induced obesity rats.

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Gao, Ya; Wang, Changjiang; Pan, Tianrong; Luo, Li

2014-02-01

Visfatin is a recently discovered adipocytokine that contributes to glucose and obesity-related conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unknown. We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats. Sprague-Dawley rats were fed a normal diet or a high-fat diet for 16 weeks to develop obesity model. The high-fat-induced obesity model rats were then randomized to metformin (MET), swimming exercise (SWI), or adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat obesity control group and a normal control group, all with 10 rats per group. Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT and SM were determined by Western Blot. Metformin and swimming exercise improved lipid profile, and increased insulin sensitivity and body weight reduction were observed. Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM. Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity.

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats.

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Yamazaki, Ricardo K; Brito, Gleisson A P; Coelho, Isabela; Pequitto, Danielle C T; Yamaguchi, Adriana A; Borghetti, Gina; Schiessel, Dalton Luiz; Kryczyk, Marcelo; Machado, Juliano; Rocha, Ricelli E R; Aikawa, Julia; Iagher, Fabiola; Naliwaiko, Katya; Tanhoffer, Ricardo A; Nunes, Everson A; Fernandes, Luiz Claudio

2011-04-28

Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Dietary supplementation with Agaricus blazei murill extract prevents diet-induced obesity and insulin resistance in rats.

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Vincent, Mylène; Philippe, Erwann; Everard, Amandine; Kassis, Nadim; Rouch, Claude; Denom, Jessica; Takeda, Yorihiko; Uchiyama, Shoji; Delzenne, Nathalie M; Cani, Patrice D; Migrenne, Stéphanie; Magnan, Christophe

2013-03-01

Dietary supplement may potentially help to fight obesity and other metabolic disorders such as insulin-resistance and low-grade inflammation. The present study aimed to test whether supplementation with Agaricus blazei murill (ABM) extract could have an effect on diet-induced obesity in rats. Wistar rats were fed with control diet (CD) or high-fat diet (HF) and either with or without supplemented ABM for 20 weeks. HF diet-induced body weight gain and increased fat mass compared to CD. In addition HF-fed rats developed hyperleptinemia and insulinemia as well as insulin resistance and glucose intolerance. In HF-fed rats, visceral adipose tissue also expressed biomarkers of inflammation. ABM supplementation in HF rats had a protective effect against body weight gain and all study related disorders. This was not due to decreased food intake which remained significantly higher in HF rats whether supplemented with ABM or not compared to control. There was also no change in gut microbiota composition in HF supplemented with ABM. Interestingly, ABM supplementation induced an increase in both energy expenditure and locomotor activity which could partially explain its protective effect against diet-induced obesity. In addition a decrease in pancreatic lipase activity is also observed in jejunum of ABM-treated rats suggesting a decrease in lipid absorption. Taken together these data highlight a role for ABM to prevent body weight gain and related disorders in peripheral targets independently of effect in food intake in central nervous system. Copyright © 2012 The Obesity Society.

CARDIAC AND BEHAVIORAL-RESPONSES OF LONG-TERM OBESE AND LEAN ZUCKER RATS TO EMOTIONAL-STRESS

NARCIS (Netherlands)

NYAKAS, C; BALKAN, B; STEFFENS, AB; BOHUS, B

1995-01-01

Obesity is known as a risk factor in stress-related cardiovascular pathology in man. The length of obesity can be an important interacting variable. Therefore, cardiac and behavioral responses to emotional stress were studied in 1-year-old, genetically obese (fa/fa) and lean (Fa/-) male Zucker rats,

Anti-obesity effect of extract from fermented Curcuma longa L. through regulation of adipogenesis and lipolysis pathway in high-fat diet-induced obese rats

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Kim, Ji Hye; Kim, Ok-Kyung; Yoon, Ho-Geun; Park, Jeongjin; You, Yanghee; Kim, Kyungmi; Lee, Yoo-Hyun; Choi, Kyung-Chul; Lee, Jeongmin; Jun, Woojin

2016-01-01

Background Even though Curcuma longa L. possesses various biological activities, it has strong flavor and taste, which decrease consumer palatability and limit industrial applications in food. Objective The present study investigates the effects of C. longa L. fermented with Aspergillus oryzae supplementation in 60% high-fat diet-induced obese rats measured by the activation of adipogenesis and lipolysis. Design Rats were divided into four groups (n=6 per group) after 1 week of acclimatization: a normal diet group comprised rats fed the AIN76A rodent diet; a high-fat diet-induced obese group with rats fed a 60% high-fat diet; a Garcinia cambogia treated group (positive control) with rats fed a 60% high-fat diet with G. cambogia 500 g/kg body weight (b.w.)/day; and an fermented C. longa L. 50% ethanolic extract treated group (FCE50) with rats fed a 60% high-fat diet with FCE50 500 g/kg b.w./day. Each group received the appropriate vehicle or sample daily by gastric intubation for 12 weeks. Results We found that FCE50 administration suppressed b.w. gain and reduced white adipose tissue weight, serum triglyceride (TG), and cholesterol in high-fat diet-induced obese rats. These results can be associated with the suppression of adipocyte differentiation and lipogenesis with a decrease in the mRNA expressions of fatty acid synthase, acetyl-CoA carboxylase, adipocyte protein 2, and lipoprotein lipase induced by FCE50 administration. In addition, FCE50 increased lipolysis and β-oxidation by up-regulating the expression of lipases such as adipose triglyceride lipase, hormone-sensitive lipase, adiponectin, and AMP-activated protein kinase. Conclusions These results suggest that FCE50 can be a candidate for the prevention of obesity via suppressing adipogenesis and promoting lipolysis. PMID:26822962

Rearing in an enriched environment attenuated hyperactivity and inattention in the Spontaneously Hypertensive Rats, an animal model of Attention-Deficit Hyperactivity Disorder.

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Botanas, Chrislean Jun; Lee, Hyelim; de la Peña, June Bryan; Dela Peña, Irene Joy; Woo, Taeseon; Kim, Hee Jin; Han, Doug Hyun; Kim, Bung-Nyun; Cheong, Jae Hoon

2016-03-01

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, characterized by symptoms of hyperactivity, inattention, and impulsivity. It is commonly treated with psychostimulants that typically begins during childhood and lasts for an extended period of time. However, there are concerns regarding the consequences of chronic psychostimulant treatment; thus, there is a growing search for an alternative management for ADHD. One non-pharmacological management that is gaining much interest is environmental enrichment. Here, we investigated the effects of rearing in an enriched environment (EE) on the expression of ADHD-like symptoms in the Spontaneously Hypertensive Rats (SHRs), an animal model of ADHD. SHRs were reared in EE or standard environment (SE) from post-natal day (PND) 21 until PND 49. Thereafter, behavioral tests that measure hyperactivity (open field test [OFT]), inattention (Y-maze task), and impulsivity (delay discounting task) were conducted. Additionally, electroencephalography (EEG) was employed to assess the effects of EE on rat's brain activity. Wistar-Kyoto (WKY) rats, the normotensive counterpart of the SHRs, were used to determine whether the effects of EE were specific to a particular genetic background. EE improved the performance of the SHRs and WKY rats in the OFT and Y-maze task, but not the delay discounting task. Interestingly, EE induced significant EEG changes in WKY rats, but not in the SHRs. These findings show that rearing environment may play a role in the expression of ADHD-like symptoms in the SHRs and that EE may be considered as a putative complementary approach in managing ADHD symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring

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Neil A Youngson

2016-01-01

Full Text Available There is now strong evidence that the paternal contribution to offspring phenotype at fertilisation is more than just DNA. However, the identity and mechanisms of this nongenetic inheritance are poorly understood. One of the more important questions in this research area is: do changes in sperm DNA methylation have phenotypic consequences for offspring? We have previously reported that offspring of obese male rats have altered glucose metabolism compared with controls and that this effect was inherited through nongenetic means. Here, we describe investigations into sperm DNA methylation in a new cohort using the same protocol. Male rats on a high-fat diet were 30% heavier than control-fed males at the time of mating (16-19 weeks old, n = 14/14. A small (0.25% increase in total 5-methyl-2Ͳ-deoxycytidine was detected in obese rat spermatozoa by liquid chromatography tandem mass spectrometry. Examination of the repetitive fraction of the genome with methyl-CpG binding domain protein-enriched genome sequencing (MBD-Seq and pyrosequencing revealed that retrotransposon DNA methylation states in spermatozoa were not affected by obesity, but methylation at satellite repeats throughout the genome was increased. However, examination of muscle, liver, and spermatozoa from male 27-week-old offspring from obese and control fathers (both groups from n = 8 fathers revealed that normal DNA methylation levels were restored during offspring development. Furthermore, no changes were found in three genomic imprints in obese rat spermatozoa. Our findings have implications for transgenerational epigenetic reprogramming. They suggest that postfertilization mechanisms exist for normalising some environmentally-induced DNA methylation changes in sperm cells.

Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not adolescent rats susceptible to diet-induced obesity

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Oginsky, Max F.; Maust, Joel D.; Corthell, John T.; Ferrario, Carrie R.

2015-01-01

Rationale Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. Objectives We determined whether there are differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity, and basal differences in the striatal neuron function in adult and adolescent obesity-prone and obesity-resistant rats. Methods Susceptible and resistant outbred rats were identified based on “junk-food” diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). Results In rats that became obese after eating “junk-food”, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ~60% at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Conclusions Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals; and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats. PMID:26612617

Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats.

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Oakes, Nicholas D; Thalén, Pia; Hultstrand, Therese; Jacinto, Severina; Camejo, Germán; Wallin, Boel; Ljung, Bengt

2005-10-01

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

Genomic and metabolic disposition of non-obese type 2 diabetic rats to increased myocardial fatty acid metabolism.

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Sriram Devanathan

Full Text Available Lipotoxicity of the heart has been implicated as a leading cause of morbidity in Type 2 Diabetes Mellitus (T2DM. While numerous reports have demonstrated increased myocardial fatty acid (FA utilization in obese T2DM animal models, this diabetic phenotype has yet to be demonstrated in non-obese animal models of T2DM. Therefore, the present study investigates functional, metabolic, and genomic differences in myocardial FA metabolism in non-obese type 2 diabetic rats. The study utilized Goto-Kakizaki (GK rats at the age of 24 weeks. Each rat was imaged with small animal positron emission tomography (PET to estimate myocardial blood flow (MBF and myocardial FA metabolism. Echocardiograms (ECHOs were performed to assess cardiac function. Levels of triglycerides (TG and non-esterified fatty acids (NEFA were measured in both plasma and cardiac tissues. Finally, expression profiles for 168 genes that have been implicated in diabetes and FA metabolism were measured using quantitative PCR (qPCR arrays. GK rats exhibited increased NEFA and TG in both plasma and cardiac tissue. Quantitative PET imaging suggests that GK rats have increased FA metabolism. ECHO data indicates that GK rats have a significant increase in left ventricle mass index (LVMI and decrease in peak early diastolic mitral annular velocity (E' compared to Wistar rats, suggesting structural remodeling and impaired diastolic function. Of the 84 genes in each the diabetes and FA metabolism arrays, 17 genes in the diabetes array and 41 genes in the FA metabolism array were significantly up-regulated in GK rats. Our data suggest that GK rats' exhibit increased genomic disposition to FA and TG metabolism independent of obesity.

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

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Iagher Fabiola

2011-04-01

Full Text Available Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG (4 mg/g body weight was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C, coconut fat-treated normal weight group (CO, fish oil-treated normal weight group (FO, obese control group (Ob, coconut fat-treated obese group (ObCO and fish oil-treated obese group (ObFO. Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30% and triacylglycerol (TG; 33% compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Implications of obesity for tendon structure, ultrastructure and biochemistry: a study on Zucker rats.

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Biancalana, Adriano; Velloso, Lício Augusto; Taboga, Sebastião Roberto; Gomes, Laurecir

2012-02-01

The extracellular matrix consists of collagen, proteoglycans and non-collagen proteins. The incidence of obesity and associated diseases is currently increasing in developed countries. Obesity is considered to be a disease of modern times, and genes predisposing to the disease have been identified in humans and animals. The objective of the present study was to compare the morphological and biochemical aspects of the deep digital flexor tendon of lean (Fa/Fa or Fa/fa) and genetically obese (fa/fa) Zucker rats. Ultrastructural analysis showed the presence of lipid droplets in both groups, whereas disorganized collagen fibril bundles were observed in obese animals. Lean animals presented a larger amount of non-collagen proteins and glycosaminoglycans than obese rats. We propose that the overweight and lesser physical activity in obese animals may have provoked the alterations in the composition and organization of extracellular matrix components but a genetic mechanism cannot be excluded. These alterations might be related to organizational and structural modifications in the collagen bundles that influence the mechanical properties of tendons and the progression to a pathological state. Copyright © 2011 Elsevier Ltd. All rights reserved.

Protective Role of Co-administration of Vitamin D in Monosodium Glutamate Induced Obesity in Female Rats.

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Nandan, Padmanabha; Nayanatara, Arun Kumar; Poojary, Roopesh; Bhagyalakshmi, K; Nirupama, M; Kini, Rekha D

2018-02-01

Obesity in females is an emerging health problem. The consumption of MSG has been considered as a risk factor for obesity. The tastemakers in Chinese and fast foods, such as fish sauce and soy sauce, contain very high levels of glutamate. The deficiency of Vitamin D is associated with obesity and metabolic syndrome. Therefore, the present study aimed to determine the effect of co-administration of Vitamin D on body weight control in MSG-induced obese rats. Eighteen adult female Wistar rats were randomly divided into three groups equally. The first group (Group I) was treated with saline served as the control; the second group (Group II) received a daily oral dose of 5 g/kg Body weight of MSG; the third group (Group III) received the same dose of MSG along with calcitriol (0.2 mcg/kg BW) for 15 days. The body weight, food, and water intake were measured. MSG treated rats showed a significant increase (P body weight, food, and water intake but significant decrease (P body weight gain in MSG-induced obese rats. Active agents in Vitamin D are useful for the prevention and treatment of obesity. Foods tested with high glutamate levels can be fortified with minute quantities of calcitriol to combat the adverse effects without compromising on the taste of the food processed. The fortification of junk foods might also combat largely prevalent Vitamin D deficiency in India. Copyright © 2018 National Medical Association. Published by Elsevier Inc. All rights reserved.

Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat

DEFF Research Database (Denmark)

Hansen, Henrik H; Jensen, Majbrit M; Overgaard, Agnete

2013-01-01

is not clarified. Tesofensine effectively induces appetite suppression in the diet-induced obese (DIO) rat partially being ascribed to an indirect stimulation of central dopamine receptor function subsequent to blocked dopamine transporter activity. This is interesting, as obese patients have reduced central......Tesofensine is a triple monoamine reuptake inhibitor which inhibits noradrenaline, 5-HT and dopamine reuptake. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong and sustained effects in obesity management...... as compared to age-matched chow-fed rats. DIO rats also exhibited a marked reduction in baseline extracellular dopamine levels in the nucleus accumbens (NAcc) and prefrontal cortex (PFC), as compared to chow-fed rats using microdialysis. While acute administration of tesofensine (2.0mg/kg) normalized accumbal...

Accumulation of ceramide in slow-twitch muscle contributes to the development of insulin resistance in the obese JCR:LA-cp rat.

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Fillmore, Natasha; Keung, Wendy; Kelly, Sandra E; Proctor, Spencer D; Lopaschuk, Gary D; Ussher, John R

2015-06-01

What is the central question of this study? The aim was to determine whether the accumulation of ceramide contributes to skeletal muscle insulin resistance in the JCR obese rat. What is the main finding and its importance? Our main new finding is that ceramides accumulate only in slow-twitch skeletal muscle in the JCR obese rat and that reducing ceramide content in this muscle type by inhibition of serine palmitoyl transferase-1 halts the progression of insulin resistance in this rat model predisposed to early development of type 2 diabetes. Our findings highlight the importance of assessing insulin signalling/sensitivity and lipid intermediate accumulation in different muscle fibre types. It has been postulated that insulin resistance results from the accumulation of cytosolic lipid metabolites (i.e. diacylglycerol/ceramide) that impede insulin signalling and impair glucose homeostasis. De novo ceramide synthesis is catalysed by serine palmitoyl transferase-1. Our aim was to determine whether de novo ceramide synthesis plays a role during development of insulin resistance in the JCR:LA-cp obese rat. Ten-week-old JCR:LA-cp obese rats were supplemented with either vehicle or the serine palmitoyl transferase-1 inhibitor l-cycloserine (360 mg l(-1) ) in their drinking water for a 2 week period, and glycaemia was assessed by meal tolerance testing. Treatment of JCR:LA-cp obese rats with l-cycloserine improved their plasma glucose and insulin levels during a meal tolerance test. Examination of muscle lipid metabolites and protein phosphorylation patterns revealed differential signatures in slow-twitch (soleus) versus fast-twitch muscle (gastrocnemius), in that ceramide levels were increased in soleus but not gastrocnemius muscles of JCR:LA-cp obese rats. Likewise, improved glycaemia in l-cycloserine-treated JCR:LA-cp obese rats was associated with enhanced Akt and pyruvate dehydrogenase signalling in soleus but not gastrocnemius muscles, probably as a result of l

An Optimized IES Method and Its Inhibitory Effects and Mechanisms on Food Intake and Body Weight in Diet-Induced Obese Rats: IES for Obesity.

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Wan, Xinyue; Yin, Jieyun; Foreman, Robert; Chen, Jiande D Z

2017-12-01

This paper aims to optimize stimulation parameters and durations for intestinal electrical stimulation (IES) and to explore the effects and mechanisms of chronic IES with optimized methodology in obesity rats. Sixteen diet-induced obese (DIO) rats were tested for food intake with four different sets of IES parameters each lasting 1 week. Then, another 12 DIO rats were used to test the effect of IES on food intake with different stimulation durations. Finally, 16 DIO rats were treated with IES or sham-IES for 4 weeks. Meal patterns, food intake, and body weight were observed. Mechanisms involving gastrointestinal motility, ghrelin, and glucagon-like peptide-1 (GLP-1) were studied. (1) Acute IES with different parameters showed different inhibitory effects on food intake, and the most effective parameters were 0.6 s on, 0.9 s off, 80 Hz, 2 ms, and 4 mA with which 26.3% decrease in food intake was noted (p fasting and postprandial plasma levels of GLP-1 but not ghrelin. Twelve-hour daily IES using optimized stimulation parameters reduces food intake and body weight in DIO rats by altering gastrointestinal motility and GLP-1. The IES methodology derived in this study may have a therapeutic potential for obesity.

Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats.

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Feigh, Michael; Andreassen, Kim V; Hjuler, Sara T; Nielsen, Rasmus H; Christiansen, Claus; Henriksen, Kim; Karsdal, Morten A

2013-07-01

Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects of oral sCT on energy and glucose homeostasis in high-fat diet (HFD)- and ovariectomy (OVX)-induced obese rats. Furthermore, the weight-regulatory and gluco-regulatory effects of short-term oral sCT intervention on HFD-induced obese rats were explored. For prevention, female rats exposed to HFD with or without OVX were treated with oral sCT for 5 weeks. As intervention, HFD-induced obese male rats were treated with oral sCT for 4 days. Body weight, food intake, and plasma glucose, insulin, and leptin levels were measured, and the clinical homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated. In addition, oral glucose tolerance was evaluated in the systemic and portal circulations. For prevention, oral sCT reduced body weight by ∼16% to 19% (P fasting glycemia (P obesity. Furthermore, oral sCT significantly reduced the incremental area under the curve for plasma glucose and insulin by ∼40% and ∼70%, respectively, during glucose tolerance testing. As intervention in HFD-induced obese rats, oral sCT reduced body weight, fasting glycemia, and insulinemia in conjunction with HOMA-IR (P obese rats, indicating the clinical usefulness of oral sCT in postmenopausal obesity-related IR and type 2 diabetes.

Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats.

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Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Teerapornpuntakit, Jarinthorn; Aeimlapa, Ratchaneevan; Chattipakorn, Nipon; Chattipakorn, Siriporn

2018-02-02

Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes. Male rats were fed a high-fat diet for 12 weeks to induce obese insulin resistance and then treated with vildagliptin for 4 weeks. The effects of the drug on bone were determined by microcomputed tomography and bone histomorphometry. Vildagliptin markedly improved insulin resistance in these obese insulin-resistant rats. It also significantly increased volumetric bone mineral density. Specifically, vildagliptin-treated obese insulin-resistant rats exhibited higher trabecular volumetric bone mineral density than vehicle-treated obese insulin-resistant rats, whereas cortical volumetric bone mineral density, cortical thickness and area were not changed. Bone histomorphometric analysis in a trabecular-rich area (i.e. tibial metaphysis) revealed greater trabecular bone volume and number and less trabecular separation without change in trabecular thickness, osteocyte lacunar area or cortical thickness in the vildagliptin-treated group. Vildagliptin had a beneficial effect on the bone of obese insulin-resistant rats with prediabetes, particularly at the trabecular site. Such benefit probably results from enhanced bone formation rather than from suppressed bone resorption. Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Liuwei Dihuang Lowers Body Weight and Improves Insulin and Leptin Sensitivity in Obese Rats

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Benjamin Perry

2012-01-01

Full Text Available The present study was aimed at investigating the efficacy and mechanism(s of action of a Chinese herbal formulation, Liuwei Dihuang (LWDH, as a prospective natural weight-lowering product. Following a 2-week acclimation period, 48 obesity-prone (OP-CD rats were divided into 4 groups (n=12 each. One group served as a positive control for obesity (OP, while the other 3 were challenged twice daily by oral gavage with total daily dosages of 500, 1500, or 3500 mg/kg BW LWDH, respectively, for 10 weeks. One group (n=12 of obesity-resistant (OR-CD rats served as the normal control group. All rats were fed the same AIN-93G diet modified to contain 60% energy from fat. The highest LWDH dose significantly reduced body weight during the last 4 weeks of treatment. Food intake was reduced beginning in week 2. The high LWDH dose lowered serum triglyceride (TG and nonesterified fatty acid (NEFA levels and body fat. Both the high and medium doses also lowered serum leptin and insulin levels. Liver function testing revealed no adverse side effects under the current experimental conditions. The results of the present study suggest that LWDH has potential as a preventive or therapeutic natural product against overweight and obesity.

Strain differences in baroceptor reflex in adult Wistar Kyoto rats

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Vitor E. Valenti

2010-01-01

Full Text Available OBJECTIVES: A subset of normotensive Sprague-Dawley rats show lower baroreflex sensitivity; however, no previous study investigated whether there are differences in baroreflex sensitivity within this subset. Our study compared baroreflex sensitivity among conscious rats of this specific subtype. METHODS: Male Wistar Kyoto (WKY rats (16 weeks old were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure (MAP and heart rate (HR. Baroreflex gain was calculated as the ratio between change in HR and MAP variation (ΔHR/ΔMAP in response to a depressor dose of sodium nitroprusside (SNP, 50 µg/kg, i.v. and a pressor dose of phenylephrine (PE, 8 µg/kg, i.v.. Rats were divided into four groups: 1 low bradycardic baroreflex (LB, baroreflex gain (BG between -1 and -2 bpm/mmHg tested with PE; 2 high bradycardic baroreflex (HB, BG < -2 bpm/mmHg tested with PE; 3 low tachycardic baroreflex (LT, BG between -1 and -2 bpm/mmHg tested with SNP and; 4 high tachycardic baroreflex (HT, BG < -2 bpm/mmHg tested with SNP. Significant differences were considered for p < 0.05. RESULTS: Approximately 37% of the rats showed a reduced bradycardic peak, bradycardic reflex and decreased bradycardic gain of baroreflex while roughly 23% had a decreased basal HR, tachycardic peak, tachycardic reflex and reduced sympathetic baroreflex gain. No significant alterations were noted with regard to basal MAP. CONCLUSION: There is variability regarding baroreflex sensitivity among WKY rats from the same laboratory.

Caloric Restriction in Lean and Obese Strains of Laboratory Rat: Effects on Body Composition, Metabolism, Growth, and Overall Health

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NEW FINDINGS: What is the central question of this study? How do lean and obese rats respond physiologically to caloric restriction? What is the main finding and its importance? Obese rats show marked benefits compared with lean animals. Reduced body fat is associated with improv...

Arcuate nucleus of hypothalamus is involved in mediating the satiety effect of electroacupuncture in obese rats.

Science.gov (United States)

Fei Wang; Tian, De Run; Tso, Patrick; Han, Ji Sheng

2011-12-01

Obesity is a major health problem in the world. Since effective remedies are rare, researchers are trying to discover new therapies for obesity, and acupuncture is among the most popular alternative approaches. This study investigated the anti-obesity mechanisms of EA, using a rat model of diet-induced obesity. After feeding with a high-fat diet for 9 weeks, a number of rats who gained weight that surpassed the maximal body weight of rats in the chow-fed group were considered obese and employed in the study. A 2 Hz EA treatment at the acupoints ST36/SP6 with the intensity increasing stepwise from 0.5-1-1.5 mA was given once a day for 30 min. Rats treated with EA showed significantly decreased food intake and reduced body weight compared with the rats in DIO and restraint group. EA treatment increased peptide levels of α-MSH and mRNA levels of its precursor POMC in the arcuate nuclear of hypothalamus (ARH) neurons. In addition, the cerebral spinal fluid (CSF) content of α-MSH was elevated by EA application. ARH lesions by monosodium glutamate abolished the inhibition effect of EA on food intake and body weight. A non-acupoint stimulation did not show the benefit effect on food intake inhibition and body weight reduction compared with restraint and ST36/SP6 EA treatment. We concluded that EA treatment at ST36/SP6 acted through ARH to significantly inhibit food intake and body weight gain when fed a high-fat diet and that the stimulation of α-MSH expression and release might be involved in the mechanism. Copyright © 2011 Elsevier Inc. All rights reserved.

Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension

International Nuclear Information System (INIS)

Dubois, E.A.; Kam, K.L.; Somsen, G.A.; Boer, G.J.; Bruin, K. de; Batink, H.D.; Pfaffendorf, M.; Royen, E.A. van; Zwieten, P.A. van

1996-01-01

The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([ 123 I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 μCi [ 123 I]MIBG. Initial myocardial uptake and washout rates of [ 123 I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular β-adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of β-adrenoceptors, indicative of increased sympathetic activity. Cardiac [ 123 I]MIBG then showed increased washouts, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [ 123 I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity noninvasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in β-adrenoceptor density were found, whereas [ 123 I]MIBG wash-out rate was increased. Thus, either [ 123 I]MIBG washout or β-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. (orig./MG)

Cardiac, Metabolic and Molecular Profiles of Sedentary Rats in the Initial Moment of Obesity

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Bruno Barcellos Jacobsen

2017-10-01

Full Text Available Abstract Background: Different types of high-fat and/or high-energy diets have been used to induce obesity in rodents. However, few studies have reported on the effects observed at the initial stage of obesity induced by high-fat feeding on cardiac functional and structural remodelling. Objective: To characterize the initial moment of obesity and investigate both metabolic and cardiac parameters. In addition, the role of Ca2+ handling in short-term exposure to obesity was verified. Methods: Thirty-day-old male Wistar rats were randomized into two groups (n = 19 each: control (C; standard diet and high-fat diet (HF, unsaturated high-fat diet. The initial moment of obesity was defined by weekly measurement of body weight (BW complemented by adiposity index (AI. Cardiac remodelling was assessed by morphological, histological, echocardiographic and papillary muscle analysis. Ca2+ handling proteins were determined by Western Blot. Results: The initial moment of obesity occurred at the 3rd week. Compared with C rats, the HF rats had higher final BW (4%, body fat (20%, AI (14.5%, insulin levels (39.7%, leptin (62.4% and low-density lipoprotein cholesterol (15.5% but did not exhibit alterations in systolic blood pressure. Echocardiographic evaluation did not show alterations in cardiac parameters. In the HF group, muscles were observed to increase their +dT/dt (C: 52.6 ± 9.0 g/mm2/s and HF: 68.0 ± 17.0 g/mm2/s; p < 0.05. In addition, there was no changes in the cardiac expression of Ca2+ handling proteins. Conclusion: The initial moment of obesity promotes alterations to hormonal and lipid profiles without cardiac damage or changes in Ca2+ handling.

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

OpenAIRE

Iagher Fabiola; Aikawa Julia; Rocha Ricelli ER; Machado Juliano; Kryczyk Marcelo; Schiessel Dalton; Borghetti Gina; Yamaguchi Adriana A; Pequitto Danielle CT; Coelho Isabela; Brito Gleisson AP; Yamazaki Ricardo K; Naliwaiko Katya; Tanhoffer Ricardo A; Nunes Everson A

2011-01-01

Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish...

Individual Differences in Cue-Induced Motivation and Striatal Systems in Rats Susceptible to Diet-Induced Obesity.

Science.gov (United States)

Robinson, Mike J F; Burghardt, Paul R; Patterson, Christa M; Nobile, Cameron W; Akil, Huda; Watson, Stanley J; Berridge, Kent C; Ferrario, Carrie R

2015-08-01

Pavlovian cues associated with junk-foods (caloric, highly sweet, and/or fatty foods), like the smell of brownies, can elicit craving to eat and increase the amount of food consumed. People who are more susceptible to these motivational effects of food cues may have a higher risk for becoming obese. Further, overconsumption of junk-foods leading to the development of obesity may itself heighten attraction to food cues. Here, we used a model of individual susceptibility to junk-foods diet-induced obesity to determine whether there are pre-existing and/or diet-induced increases in attraction to and motivation for sucrose-paired cues (ie, incentive salience or 'wanting'). We also assessed diet- vs obesity-associated alterations in mesolimbic function and receptor expression. We found that rats susceptible to diet-induced obesity displayed heightened conditioned approach prior to the development of obesity. In addition, after junk-food diet exposure, those rats that developed obesity also showed increased willingness to gain access to a sucrose cue. Heightened 'wanting' was not due to individual differences in the hedonic impact ('liking') of sucrose. Neurobiologically, Mu opioid receptor mRNA expression was lower in striatal 'hot-spots' that generate eating or hedonic impact only in those rats that became obese. In contrast, prolonged exposure to junk-food resulted in cross-sensitization to amphetamine-induced locomotion and downregulation of striatal D2R mRNA regardless of the development of obesity. Together these data shed light on individual differences in behavioral and neurobiological consequences of exposure to junk-food diets and the potential contribution of incentive sensitization in susceptible individuals to greater food cue-triggered motivation.

Individual Differences in Cue-Induced Motivation and Striatal Systems in Rats Susceptible to Diet-Induced Obesity

Science.gov (United States)

Robinson, Mike JF; Burghardt, Paul R; Patterson, Christa M; Nobile, Cameron W; Akil, Huda; Watson, Stanley J; Berridge, Kent C; Ferrario, Carrie R

2015-01-01

Pavlovian cues associated with junk-foods (caloric, highly sweet, and/or fatty foods), like the smell of brownies, can elicit craving to eat and increase the amount of food consumed. People who are more susceptible to these motivational effects of food cues may have a higher risk for becoming obese. Further, overconsumption of junk-foods leading to the development of obesity may itself heighten attraction to food cues. Here, we used a model of individual susceptibility to junk-foods diet-induced obesity to determine whether there are pre-existing and/or diet-induced increases in attraction to and motivation for sucrose-paired cues (ie, incentive salience or ‘wanting’). We also assessed diet- vs obesity-associated alterations in mesolimbic function and receptor expression. We found that rats susceptible to diet-induced obesity displayed heightened conditioned approach prior to the development of obesity. In addition, after junk-food diet exposure, those rats that developed obesity also showed increased willingness to gain access to a sucrose cue. Heightened ‘wanting’ was not due to individual differences in the hedonic impact (‘liking’) of sucrose. Neurobiologically, Mu opioid receptor mRNA expression was lower in striatal ‘hot-spots’ that generate eating or hedonic impact only in those rats that became obese. In contrast, prolonged exposure to junk-food resulted in cross-sensitization to amphetamine-induced locomotion and downregulation of striatal D2R mRNA regardless of the development of obesity. Together these data shed light on individual differences in behavioral and neurobiological consequences of exposure to junk-food diets and the potential contribution of incentive sensitization in susceptible individuals to greater food cue-triggered motivation. PMID:25761571

Repeated stress exposure causes strain-dependent shifts in the behavioral economics of cocaine in rats

NARCIS (Netherlands)

Groblewski, Peter A.; Zietz, Chad; Willuhn, Ingo; Phillips, Paul E. M.; Chavkin, Charles

2015-01-01

Cocaine-experienced Wistar and Wistar Kyoto (WKY) rats received four daily repeated forced swim stress sessions (R-FSS), each of which preceded 4-hour cocaine self-administration sessions. Twenty-four hours after the last swim stress, cocaine valuation was assessed during a single-session threshold

Supplementation of Syzygium cumini seed powder prevented obesity, glucose intolerance, hyperlipidemia and oxidative stress in high carbohydrate high fat diet induced obese rats.

Science.gov (United States)

Ulla, Anayt; Alam, Md Ashraful; Sikder, Biswajit; Sumi, Farzana Akter; Rahman, Md Mizanur; Habib, Zaki Farhad; Mohammed, Mostafe Khalid; Subhan, Nusrat; Hossain, Hemayet; Reza, Hasan Mahmud

2017-06-02

Obesity and related complications have now became epidemic both in developed and developing countries. Cafeteria type diet mainly composed of high fat high carbohydrate components which plays a significant role in the development of obesity and metabolic syndrome. This study investigated the effect of Syzygium cumini seed powder on fat accumulation and dyslipidemia in high carbohydrate high fat diet (HCHF) induced obese rats. Male Wistar rats were fed with HCHF diet ad libitum, and the rats on HCHF diet were supplemented with Syzygium cumini seed powder for 56 days (2.5% w/w of diet). Oral glucose tolerance test, lipid parameters, liver marker enzymes (AST, ALT and ALP) and lipid peroxidation products were analyzed at the end of 56 days. Moreover, antioxidant enzyme activities were also measured in all groups of rats. Supplementation with Syzygium cumini seed powder significantly reduced body weight gain, white adipose tissue (WAT) weights, blood glucose, serum insulin, and plasma lipids such as total cholesterol, triglyceride, LDL and HDL concentration. Syzygium cumini seed powder supplementation in HCHF rats improved serum aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP) activities. Syzygium cumini seed powder supplementation also reduced the hepatic thiobarbituric acid reactive substances (TBARS) and elevated the antioxidant enzyme superoxide dismutase (SOD) and catalase (CAT) activities as well as increased glutathione (GSH) concentration. In addition, histological assessment showed that Syzygium cumini seed powder supplementation prevented inflammatory cell infiltration; fatty droplet deposition and fibrosis in liver of HCHFD fed rats. Our investigation suggests that Syzygium cumini seed powder supplementation prevents oxidative stress and showed anti-inflammatory and antifibrotic activity in liver of HCHF diet fed rats. In addition, Syzygium cumini seed powder may be beneficial in ameliorating insulin

Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

International Nuclear Information System (INIS)

Sung, Jin Young; Choi, Hyoung Chul

2011-01-01

Highlights: → Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. → Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. → Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. → Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. → Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Sung, Jin Young [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

2011-05-06

Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

Influence of chronic captopril treatment on norepinephrine-induced vasoconstriction in SHR and WKY : In vivo study

Czech Academy of Sciences Publication Activity Database

Pintérová, Mária; Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

2008-01-01

Roč. 26, Suppl.1 (2008), S174-S174 ISSN 0263-6352. [Scientific Meeting International Society of Hypertension /22./ , Scientific Meeting European Society of Hypertension /18./. 14.06.2008-19.06.2008, Berlin] Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * captopril teratment * norepinephrine-induced vasoconstriction * SHR and WKY Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

Antiobesity Effects of the Ethanol Extract of Laminaria japonica Areshoung in High-Fat-Diet-Induced Obese Rat

Directory of Open Access Journals (Sweden)

Woong Sun Jang

2013-01-01

Full Text Available Laminaria japonica Areshoung, a widely consumed marine vegetable, has traditionally been used in Korean maternal health. The present study investigated the antiobesity effects of Laminaria japonica Areshoung ethanol extract (LE and its molecular mechanism in high-fat-diet-induced obese rats. Six-week-old Sprague-Dawley male rats were separately fed a normal diet or a high-calorie high-fat diet for 6 weeks; then they were treated with LE or tea catechin for another 6 weeks. LE administration significantly decreased the body weight gain, fat-pad weights, and serum and hepatic lipid levels in HD-induced obese rats. The histological analysis revealed that LE-treated group showed a significantly decreased number of lipid droplets and size of adipocytes compared to the HD group. To elucidate the mechanism of action of LE, the levels of genes and proteins involved in obesity were measured in the liver and skeletal muscle. LE treatment resulted in an increased expression of fatty acid oxidation and thermogenesis-related genes in obese rats. Conversely, the expression of the fat intake-related gene (ACC2 and lipogenesis-related genes was reduced by LE treatment. Additionally, LE treatment increased the phosphorylation of AMP-activated protein kinase and its direct downstream protein, acetyl coenzyme A carboxylase, which is one of the rate-limiting enzymes in fatty acid synthesis pathway. These findings demonstrate that LE treatment has a protective effect against a high-fat-diet-induced obesity in rats through regulation of expression of genes and proteins involved in lipolysis and lipogenesis.

Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats

Science.gov (United States)

Zhang, Yan; Su, Linan; Zhang, Yunrong; Wang, Qiang; Yang, Dachun; Li, De; Yang, Yongjian; Ma, Shuangtao

2017-01-01

Background Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR). Methods SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure. Results We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group. Conclusions Radiofrequency

Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

Directory of Open Access Journals (Sweden)

María Eugenia Hernandez

2013-01-01

Full Text Available Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily, chemical stress (hydrocortisone treatment, 50 mg/Kg weight, mixed stress (restraint plus hydrocortisone, or control treatment (without stress for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats.

Science.gov (United States)

Briant, Linford J B; Stalbovskiy, Alexey O; Nolan, Matthew F; Champneys, Alan R; Pickering, Anthony E

2014-12-01

Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15-30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension. Copyright © 2014 the American Physiological Society.

Administration of dried Aloe vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats.

Science.gov (United States)

Misawa, Eriko; Tanaka, Miyuki; Nabeshima, Kazumi; Nomaguchi, Kouji; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

2012-01-01

The aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity.

Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke

OpenAIRE

Valenti, Vitor E.; Abreu, Luiz Carlos de; Fonseca, Fernando L. A.; Adami, Fernando; Sato, Monica A.; Vanderlei, Luiz Carlos M.; Ferreira, Lucas Lima; Rodrigues, Luciano M.; Ferreira, Celso

2013-01-01

OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4...

Relationship between lipogenesis, ketogenesis, and malonyl-CoA content in isolated hepatocytes from the obese Zucker rat adapted to a high-fat diet.

Science.gov (United States)

Malewiak, M I; Griglio, S; Le Liepvre, X

1985-07-01

The relationship between lipogenesis and ketogenesis and the concentration of malonyl coenzyme A (CoA) was investigated in hepatocytes from adult obese Zucker rats and their lean littermates fed either a control low-fat diet or a high-fat diet (30% lard in weight). With the control diet, lipogenesis--although strongly inhibited in the presence of either 1 mmol/L oleate, 10(-6) mol/L glucagon or 0.1 mmol/L TOFA (a hypolipidemic drug)--remained about fifteen-fold higher in the obese rats than in the lean rats. In contrast, ketogenesis under some conditions (oleate + TOFA) was not significantly lower (30%) as compared with the lean rats. After adaptation to the high-fat diet, lipogenesis was depressed fourfold in the lean rats and ninefold in the obese ones; however its magnitude remained significantly higher in the latter, namely at a value close to that measured in control-fed lean rats. Ketogenesis was comparable in lean and obese rats and much higher in the presence of 1 mmol/L oleate than of 0.3 mmol/L oleate, whereas lipogenesis did not vary with increasing oleate concentration in the medium. Acetyl-CoA carboxylase activity measured in liver homogenates was higher in the obese group, but was stepwise inhibited by increasing concentrations of oleyl-CoA regardless of the diet for both lean and obese rats, thus showing no abnormality of in vitro responsiveness to this inhibitor. With the control diet, hepatocyte malonyl-CoA levels were significantly higher in the obese rats, both in the basal state and after inhibition of lipogenesis by oleate and TOFA.(ABSTRACT TRUNCATED AT 250 WORDS)

Renovascular hypertension in spontaneous hypertensive rats: an experimental model of renal artery stenosis superimposed on essential hypertension.

Science.gov (United States)

Rosenthal, T; Bass, A; Grossman, E; Shani, M; Griffel, B; Adar, R

1987-09-01

Renovascular hypertension superimposed on essential hypertension, a condition encountered in the elderly, was studied. An experimental animal model consisting of a two-kidney one-clip Goldblatt preparation in the spontaneous hypertensive (SHR) rat, that would simulate this condition, was designed. A 0.25 mm silver clip was placed on the left renal artery of SHR male rats. The same procedure performed on WKY rats served as control. All experiments were performed on low, normal, and rich sodium diet. Systolic blood pressure (BP) was measured by tail-cuff method. Plasma renin concentration (PRC) was determined before and after clipping of the renal artery. Results were as follows: Mean systolic BP increased significantly in clipped rats fed with normal and rich sodium diets. SHR showed an increase from 144 +/- 3 (mean + s.e.m.) to 168 +/- 3 mmHg, and WKY rats showed an increase from 120 +/- 2 to 139 +/- 5 mmHg. There was a two- to threefold rise in PRC. A low-salt diet given prior to clipping prevented the appearance of renovascular hypertension despite a significant rise in PRC. We concluded that renal artery narrowing plays a significant role in the rise of BP in the basically essential type of hypertension.

Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

OpenAIRE

Suhana Samat; Francis Kanyan Enchang; Fuzina Nor Hussein; Wan Iryani Wan Ismail

2017-01-01

Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using h...

Evaluation of anti-obesity activity of duloxetine in comparison with sibutramine along with its anti-depressant activity: an experimental study in obese rats.

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Chudasama, H P; Bhatt, P A

2009-11-01

5-HT and noradrenaline are important neurotransmitters that control increase in body mass and are involved in the pathophysiology of obesity and depression. Sibutramine, an established anti-obesity agent, and duloxetine, an anti-depressant agent, are serotonin noradrenaline reuptake inhibitors (SNRIs). The objective of the present study was to compare the anti-obesity effect of duloxetine with sibutramine along with its effect on blood pressure and depression in obese rats. The secondary objective of the study was to determine if a relationship exists between obesity and depression. Obesity was induced by high-fat diet (HFD) in healthy male Sprague-Dawley rats. After 5 weeks of feeding HFD, animals were overweight (17.57%) with high food intake (57.15%) in comparison with normal animals. These obese animals were treated with duloxetine (30 mg x kg(-1), p.o.) and sibutramine (5 mg x kg(-1), p.o.) for 4 weeks. Control animals were treated with duloxetine alone (30 mg x kg(-1), p.o.). Our results depict that duloxetine was as effective as sibutramine in reducing food intake, body mass, and relative adiposity, and increasing rectal temperature with an added advantage of decreasing blood pressure, which sibutramine failed to do. Besides reduction in body mass, unlike sibutramine, duloxetine improved depressive state as evaluated by despair swimming test, tail suspension test, and open field test, speculating its use as an anti-obesity agent in obese-depressive animals. Since obese control animals reflected decreased locomotor activity, a positive relationship can be speculated to exist between obesity and depression. Further studies on various antidepressant models are required to confirm this relationship.

High dietary fat-induced obesity in Wistar rats and type 2 diabetes in nonobese Goto-Kakizaki rats differentially affect retinol binding protein 4 expression and vitamin A metabolism.

Science.gov (United States)

Shirai, Tomomi; Shichi, Yuta; Sato, Miyuki; Tanioka, Yuri; Furusho, Tadasu; Ota, Toru; Tadokoro, Tadahiro; Suzuki, Tsukasa; Kobayashi, Ken-Ichi; Yamamoto, Yuji

2016-03-01

Obesity is a major risk factor for type 2 diabetes, which is caused mainly by insulin resistance. Retinol binding protein 4 (RBP4) is the only specific transport protein for retinol in the serum. RBP4 level is increased in the diabetic state and high-fat condition, indicating that retinol metabolism may be affected under these conditions. However, the precise effect of diabetes and high fat-induced obesity on retinol metabolism is unknown. In this study, we examined differences in retinol metabolite levels in rat models of diet-induced obesity and type 2 diabetes (Goto-Kakizaki [GK] rat). Four-week-old male Wistar and GK rats were given either a control diet (AIN-93G) or a high-fat diet (HFD, 40% fat kJ). After 15 weeks of feeding, the RBP4 levels increased by 2-fold in the serum of GK rats but not HFD-fed rats. The hepatic retinol concentration of HFD-fed rats was approximately 50% that of the controls (P type 2 diabetes mellitus. Copyright © 2016 Elsevier Inc. All rights reserved.

Investigation of brain-derived neurotrophic factor (BDNF) gene expression in hypothalamus of obese rats: Modulation by omega-3 fatty acids.

Science.gov (United States)

Abdel-Maksoud, Sahar M; Hassanein, Sally I; Gohar, Neveen A; Attia, Saad M M; Gad, Mohamed Z

2017-10-01

The aim of this study was investigating the effect of omega-3 fatty acids (ω-3 FAs) on brain-derived neurotrophic factor (BDNF) gene expression, using in vivo and in vitro models, to unravel the potential mechanisms of polyunsaturated fatty acids use in obesity. Twenty-nine Sprague-Dawley rats were divided into three groups; lean controls fed normal chow diet for 14 weeks, obese controls fed 60% of their diet as saturated fats for 14 weeks, and ω-3 FAs-treated rats fed 60% saturated fat diet for 14 weeks with concomitant oral administration of 400 mg/kg/day ω-3 FAs, mainly docosahexaenoic acid and EPA, from week 12 to week 14. For the in vitro experiment, hypothalamic cells from six obese rats were cultured in the presence of different concentrations of ω-3 FAs to determine its direct effect on BDNF expression. In vivo results showed that obesity has negative effect on BDNF gene expression in rat hypothalamus that was reversed by administration of ω-3 FAs. Obese rats showed hypercholesterolemia, hypertriglyceridemia, normoinsulinemia, hyperglycemia and hyperleptinemia. Treatment with ω-3 FAs showed significant decrease in serum total cholesterol and TAG. Also serum glucose level and HOMA index were decreased significantly. In vitro results demonstrated the increase in BDNF expression by ω-3 FAs in a dose-dependent manner. Obesity causes down-regulation of BDNF gene expression that can be reversed by ω-3 FAs treatment, making them an interesting treatment approach for obesity and metabolic disease.

Cerebral markers of the serotonergic system in rat models of obesity and after Roux-en-Y gastric bypass

DEFF Research Database (Denmark)

Ratner, Cecilia; Ettrup, Anders; Bueter, Marco

2012-01-01

Food intake and body weight are regulated by a complex system of neural and hormonal signals, of which the anorexigenic neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) is central. In this study, rat models of obesity and weight loss intervention were compared with regard to several 5-HT......DIO as compared to pgDR rats corresponds to what is reported in overweight humans and suggests that the dysfunctions of the 5-HT system associated with overeating or propensity to become overweight are polygenically determined. Our results support that the obesity-prone rat model has high translational value...... and suggests that susceptibility to develop obesity is associated with changed 5-HT tone in the brain that may also regulate hedonic aspects of feeding....

High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats

Science.gov (United States)

Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

2013-01-01

Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (−9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

Roux-en-Y gastric bypass surgery suppresses hypothalamic PTP1B protein level and alleviates leptin resistance in obese rats.

Science.gov (United States)

Liu, Jia-Yu; Mu, Song; Zhang, Shu-Ping; Guo, Wei; Li, Qi-Fu; Xiao, Xiao-Qiu; Zhang, Jun; Wang, Zhi-Hong

2017-09-01

The present study aimed to explore the effect of Roux-en-Y gastric bypass (RYGB) surgery on protein tyrosine phosphatase 1B (PTP1B) expression levels and leptin activity in hypothalami of obese rats. Obese rats induced by a high-fat diet (HFD) that underwent RYGB (n=11) or sham operation (SO, n=9), as well as an obese control cohort (Obese, n=10) and an additional normal-diet group (ND, n=10) were used. Food efficiency was measured at 8 weeks post-operation. Plasma leptin levels were evaluated and hypothalamic protein tyrosine phosphatase 1B (PTP1B) levels and leptin signaling activity were examined at the genetic and protein levels. The results indicated that food efficiency was typically lower in RYGB rats compared with that in the Obese and SO rats. In the RYGB group, leptin receptor expression and proopiomelanocortin was significantly higher, while Neuropeptide Y levels were lower than those in the Obese and SO groups. Furthermore, the gene and protein expression levels of PTP1B in the RYGB group were lower, while levels of phosphorylated signal transducer and activator of transcription 3 protein were much higher compared with those in the Obese and SO groups. In conclusion, RYGB surgery significantly suppressed hypothalamic PTP1B protein expression. PTP1B regulation may partially alleviate leptin resistance.

Sequential change of BMIPP uptake with age in spontaneously hypertensive rat model

International Nuclear Information System (INIS)

Mochizuki, Takafumi; Tsukamoto, Eriko; Ono, Tomohide

1997-01-01

Changes in myocardial perfusion and metabolism are often associated with myocardial hypertrophy, but there are few reports describing the serial assessment of fatty acid metabolism in hypertrophic myocardium. The aim of this study is to assess fatty acid metabolism serially in hypertrophic myocardium in spontaneously hypertensive rats (SHR) with 125 I-BMIPP, a branched fatty acid analog. SHR and Wistar-Kyoto rats (WKY) as the control were divided into 4 groups (12, 15, 18 and 51 weeks after birth). The heart was extracted 10 minutes after intravenous injection of 125 I-BMIPP and 201 Tl at the same time. The accumulation of each radiotracer in the myocardium was counted with a well gamma counter. In addition, 125 I-BMIPP uptake was corrected by 201 Tl uptake (B/T). The heart weight/body weight ratio was significantly higher in SHR than that in WKY (p 125 I-BMIPP uptake tended to be significantly reduced in SHR (12 weeks; 2.373±0.212, 18 weeks; 1.380±0.047: mean±SE, p 125 I-BMIPP and 201 Tl. (author)

Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats.

Science.gov (United States)

Legette, Leecole L; Luna, Arlyn Y Moreno; Reed, Ralph L; Miranda, Cristobal L; Bobe, Gerd; Proteau, Rosita R; Stevens, Jan F

2013-07-01

Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9 mg/kg BW for 6 weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3 weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet for the last 3 weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay kits. Plasma and liver tissue levels of XN and its metabolites were determined by liquid-chromatography tandem mass spectrometry. Plasma and liver tissue levels of xanthohumol were similar between low and medium dose groups and significantly (peffect on body weight and plasma glucose levels. The highest dose group (n=6) had significantly lower plasma glucose levels compared to the control group (n=6) in male but not female rats. There was also a significant decrease in body weight for male rats in the highest dose group (16.9 mg/kg BW) compared to rats that received no xanthohumol, which was also not seen for female rats. Plasma cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not affected by treatment. The findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome. Copyright © 2012. Published by Elsevier Ltd.

Effect of feeding a high-fat diet independently of caloric intake on reproductive function in diet-induced obese female rats

Science.gov (United States)

Hussain, Mona A.; Abogresha, Noha M.; Tamany, Dalia A.; Lotfy, Mariam

2016-01-01

Introduction Globally, the prevalence of overweight and obesity is increasing, predisposing females to health hazards including compromised reproductive capacity. Our objective was to investigate the effect of ad libitum, isocalorically and hypocalorically restricted high-fat diet (HFD) feeding on reproductive function in diet-induced obese female rats. Material and methods Twenty female albino Sprague Dawley rats were used; 5 rats were kept on a standard pellet animal diet to serve as a control group (A) and 15 rats were fed a HFD for 9 weeks to induce obesity. The HFD fed animals were equally divided into three groups: an ad libitum HFD group (B), an isocalorically restricted HFD group (C), and a hypocalorically restricted HFD group (D). Estrous cyclicity, hormonal levels, ovarian histopathology and caspase-3 immunoreactivity were evaluated. Results The HFD-fed rats in groups B, C and D had significant irregularity in estrous cyclicity Vs group A (p = 0.001, 0.003 and 0.034 respectively). Groups C and D had significant reduction in serum progesterone level (p = 0.006 and 0.018 Vs A). Isocaloric restriction of HFD feeding significantly increased serum LH. Groups B and C had a significant increase in caspase-3 expression in the ovary (p < 0.001). Conclusions Ad libitum HFD interfered with the normal estrous cycle and enhanced apoptosis of luteal cells in obese female rats. The HFD restriction interfered with the normal estrous cycle and caused functional insufficiency of the corpus luteum in obese female rats. These results suggest that HFD feeding determinately affects female reproductive function independently of caloric intake. PMID:27478474

The impact of obesity in the cardiac lipidome and its consequences in the cardiac damage observed in obese rats.

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Marín-Royo, Gema; Martínez-Martínez, Ernesto; Gutiérrez, Beatriz; Jurado-López, Raquel; Gallardo, Isabel; Montero, Olimpio; Bartolomé, Mª Visitación; Román, José Alberto San; Salaices, Mercedes; Nieto, María Luisa; Cachofeiro, Victoria

To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O 2 ), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals. Cardiac lipid profile analysis showed a significant increase in triglycerides, especially those enriched with palmitic, stearic, and arachidonic acid. An increase in levels of diacylglycerol (DAG) was also observed. No changes in cardiac levels of diacyl phosphatidylcholine, or even a reduction in total levels of diacyl phosphatidylethanolamine, diacyl phosphatidylinositol, and sphingomyelins (SM) was observed in HFD, as compared with control animals. After adjustment for other variables (oxidative stress, HOMA, cardiac hypertrophy), total levels of DAG were independent predictors of cardiac fibrosis while the levels of total SM were independent predictors of the cardiac levels of GLUT 4. These data suggest that obesity has a significant impact on cardiac lipid composition, although it does not modulate the different species in a similar manner. Nonetheless, these changes are likely to participate in the cardiac damage in the context of obesity, since total DAG levels can facilitate the development of cardiac fibrosis, and SM levels predict GLUT4 levels. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Obesity and type 2 diabetes in rats are associated with altered brain glycogen and amino-acid homeostasis

DEFF Research Database (Denmark)

Sickmann, Helle M; Waagepetersen, Helle S; Schousboe, Arne

2010-01-01

Obesity and type 2 diabetes have reached epidemic proportions; however, scarce information about how these metabolic syndromes influence brain energy and neurotransmitter homeostasis exist. The objective of this study was to elucidate how brain glycogen and neurotransmitter homeostasis are affected...... by these conditions. [1-(13)C]glucose was administered to Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rats. Sprague-Dawley (SprD), Zucker lean (ZL), and ZDF lean rats were used as controls. Several brain regions were analyzed for glycogen levels along with (13)C-labeling and content of glutamate, glutamine...... of glutamine and glutamate were decreased in the cerebellum of the ZO and the ZDF rats. Glycogen levels were also lower in this region. These results suggest that the obese and type 2 diabetic models were associated with lower brain glucose metabolism. Glucose metabolism through the TCA cycle was more...

Roux-en-Y gastric bypass increases intravenous ethanol self-administration in dietary obese rats.

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James E Polston

Full Text Available Roux-en-Y gastric bypass surgery (RYGB is an effective treatment for severe obesity. Clinical studies however have reported susceptibility to increased alcohol use after RYGB, and preclinical studies have shown increased alcohol intake in obese rats after RYGB. This could reflect a direct enhancement of alcohol's rewarding effects in the brain or an indirect effect due to increased alcohol absorption after RGYB. To rule out the contribution that changes in alcohol absorption have on its rewarding effects, here we assessed the effects of RYGB on intravenously (IV administered ethanol (1%. For this purpose, high fat (60% kcal from fat diet-induced obese male Sprague Dawley rats were tested ~2 months after RYGB or sham surgery (SHAM using both fixed and progressive ratio schedules of reinforcement to evaluate if RGYB modified the reinforcing effects of IV ethanol. Compared to SHAM, RYGB rats made significantly more active spout responses to earn IV ethanol during the fixed ratio schedule, and achieved higher breakpoints during the progressive ratio schedule. Although additional studies are needed, our results provide preliminary evidence that RYGB increases the rewarding effects of alcohol independent of its effects on alcohol absorption.

Effects of proportions of dietary macronutrients on glucocorticoid metabolism in diet-induced obesity in rats.

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Roland H Stimson

2010-01-01

Full Text Available Tissue glucocorticoid levels in the liver and adipose tissue are regulated by regeneration of inactive glucocorticoid by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1 and inactivation by 5alpha- and 5beta-reductases. A low carbohydrate diet increases hepatic 11beta-HSD1 and reduces glucocorticoid metabolism during weight loss in obese humans. We hypothesized that similar variations in macronutrient proportions regulate glucocorticoid metabolism in obese rats. Male Lister Hooded rats were fed an obesity-inducing ad libitum 'Western' diet (37% fat, n = 36 for 22 weeks, then randomised to continue this diet (n = 12 or to switch to either a low carbohydrate (n = 12 or a moderate carbohydrate (n = 12 diet for the final 8 weeks. A parallel lean control group were fed an ad libitum control diet (10% fat, n = 12 throughout. The low and moderate carbohydrate diets decreased hepatic 11beta-HSD1 mRNA compared with the Western diet (both 0.7+/-0.0 vs 0.9+/-0.1 AU; p<0.01, but did not alter 11beta-HSD1 in adipose tissue. 5Alpha-reductase mRNA was increased on the low carbohydrate compared with the moderate carbohydrate diet. Compared with lean controls, the Western diet decreased 11beta-HSD1 activity (1.6+/-0.1 vs 2.8+/-0.1 nmol/mcg protein/hr; p<0.001 and increased 5alpha-reductase and 5beta-reductase mRNAs (1.9+/-0.3 vs 1.0+/-0.2 and 1.6+/-0.1 vs 1.0+/-0.1 AU respectively; p<0.01 in the liver, and reduced 11beta-HSD1 mRNA and activity (both p<0.01 in adipose tissue. Although an obesity-inducing high fat diet in rats recapitulates the abnormal glucocorticoid metabolism associated with human obesity in liver (but not in adipose tissue, a low carbohydrate diet does not increase hepatic 11beta-HSD1 in obese rats as occurs in humans.

Hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways.

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Uebanso, Takashi; Taketani, Yutaka; Fukaya, Makiko; Sato, Kazusa; Takei, Yuichiro; Sato, Tadatoshi; Sawada, Naoki; Amo, Kikuko; Harada, Nagakatsu; Arai, Hidekazu; Yamamoto, Hironori; Takeda, Eiji

2009-07-01

The mechanism by which replacement of some dietary carbohydrates with protein during weight loss favors lipid metabolism remains obscure. In this study, we investigated the effect of an energy-restricted, high-protein/low-carbohydrate diet on lipid metabolism in obese rats. High-sucrose-induced obese rats were assigned randomly to one of two energy-restricted dietary interventions: a carbohydrate-based control diet (CD) or a high-protein diet (HPD). Lean rats of the same age were assigned as normal control. There was significantly greater improvement in fatty liver and hypertriglyceridemia with the HPD diet relative to the CD diet. Expression of genes regulated by fibroblast growth factor-21 (FGF21) and involved in liver lipolysis and lipid utilitization, such as lipase and acyl-CoA oxidase, increased in obese rats fed the HPD. Furthermore, there was an inverse correlation between levels of FGF21 gene expression (regulated by glucagon/insulin balance) and increased triglyceride concentrations in liver from obese rats. Expression of hepatic stearoyl-CoA desaturase-1 (SCD1), regulated primarily by the dietary carbohydrate, was also markedly reduced in the HPD group (similar to plasma triglyceride levels in fasting animals) relative to the CD group. In conclusion, a hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia effectively relative to a carbohydrate diet. The two cellular pathways at work behind these benefits include stimulation of hepatic lipolysis and lipid utilization mediated by FGF21 and reduction of hepatic VLDL-TG production by SCD1 regulation.

Obesity reduces bone density through activation of PPAR gamma and suppression of Wnt/Beta-Catenin in rapidly growing male rats

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The relationship between obesity and skeletal development remains largely ambiguous. In this report, total enteral nutrition (TEN) was used to feed growing male rats intragastrically, with a high 45% fat diet (HFD) to induce obesity. We found that fat mass was increased (P<0.05) compared to rats fed...

Polyphenol-Rich Extract of Syzygium cumini Leaf Dually Improves Peripheral Insulin Sensitivity and Pancreatic Islet Function in Monosodium L-Glutamate-Induced Obese Rats

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Sanches, Jonas R.; França, Lucas M.; Chagas, Vinicyus T.; Gaspar, Renato S.; dos Santos, Kayque A.; Gonçalves, Luciana M.; Sloboda, Deborah M.; Holloway, Alison C.; Dutra, Richard P.; Carneiro, Everardo M.; Cappelli, Ana Paula G.; Paes, Antonio Marcus de A.

2016-01-01

Syzygium cumini (L.) Skeels (Myrtaceae) has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed, and pulp-fruit, however. there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc) on lean and monosodium L-glutamate (MSG)-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg) or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a twofold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10–1000 μg/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E β-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating β-cell insulin release, which was associated

Polyphenol-rich extract of Syzygium cumini leaf dually improves peripheral insulin sensitivity and pancreatic islet function in monosodium L-glutamate-induced obese rats

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Jonas Rodrigues Sanches

2016-03-01

Full Text Available Syzygium cumini (L. Skeels (Myrtaceae has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed and pulp-fruit, however there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc on lean and monosodium L-glutamate (MSG-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a 2-fold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10 – 1000 ug/mL increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E beta cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating beta cell insulin release

Benazepril, an angiotensin-converting enzyme inhibitor, alleviates renal injury in spontaneously hypertensive rats by inhibiting advanced glycation end-product-mediated pathways.

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Liu, Xue-Ping; Pang, Yue-Jiu; Zhu, Wei-Wei; Zhao, Ting-Ting; Zheng, Min; Wang, Yi-Bing; Sun, Zhi-Jian; Sun, Siao-Jing

2009-03-01

1. Advanced glycation end-products (AGE) and their receptors (RAGE) have been implicated in renal damage in diabetes. The aim of the present study was to investigate the effects of benazepril, an angiotensin-converting enzyme inhibitor (ACEI), on the formation of AGE, the expression RAGE and other associated components in the oxidative stress pathway in spontaneously hypertensive rats (SHR). 2. Groups of SHR were treated with or without 10 mg/kg per day benazepril for 12 weeks. Systolic blood pressure (SBP) and angiotensin (Ang) II levels were evaluated in SHR and control Wistar-Kyoto (WKY) rats. Renal function was investigated by determining levels of proteinuria and glomerulosclerosis. Furthermore, reactive oxygen species (ROS) in the rat renal cortex were analysed using an H(2)O(2)-based hydroxyl radical-detection assay and the renal content of AGE, RAGE, NADPH oxidase p47phox, nuclear factor (NF)-kappaB p65, phosphorylated (p-) NF-kappaB p65, vascular cell adhesion molecule (VCAM)-1 and transforming growth factor (TGF)-beta1 was determined by immunohistochemistry, quantitative real-time polymerase chain reaction and western blot analysis. 3. Treatment with benazepril inhibited the formation of AngII, reduced SBP and alleviated renal lesions in SHR compared with both untreated SHR and control WKY rats. Benazepril treatment significantly suppressed the accumulation of AGE and expression of RAGE in the kidney of SHR. In addition, benazepril treatment reduced the upregulation of NADPH oxidase p47phox, ROS generation and NF-kappaB p65, p-NF-kappaB p65, VCAM-1 and TGF-beta1 expression in the kidney of SHR compared with both untreated SHR and control WKY rats. 4. The results of the present study provide new insights into the regulation by the renin-angiotensin system of AGE-RAGE, oxidative stress and nephropathy, increasing our understanding of the role of the RAS in nephropathy.

Effects of music composed by Mozart and Ligeti on blood pressure and heart rate circadian rhythms in normotensive and hypertensive rats.

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Lemmer, Björn

2008-11-01

There is continuing discussion on the effect of music ("Mozart effect") on numerous functions in man and experimental animals. Radiotelemetry now allows one to monitor cardiovascular functions in freely-moving unrestrained experimental animals. Radiotelemetry was used to monitor systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and motor activity (MA) in male normotensive WKY and hypertensive SHR animals. Rats were synchronized to a 12 h light (L): 12 h dark (D) regimen in an isolated, ventilated, light-controlled, sound-isolated animal container. Music (Mozart, Symphony # 40; Ligeti, String Quartet # 2) were played for 2 h at 75 dB in the animal cabin starting at the onset of L or D in a cross-over design. Data were collected every 5 min for 24 h under control conditions and during and after music. In addition, plasma concentrations of norepinephrine (NE) were determined in unrestrained animals at 3 h intervals over 24 h. In both WKY and SHR, highly significant circadian rhythms were obtained in SBP, DBP, HR, and MA under control conditions; HR was lower and BP higher in SHR than in WKY. NE was circadian rhythmic in both strains with higher values in D; the increase in NE with immobilization was much more pronounced in SHR than in WKY. The music of Mozart had no effect on either parameter in WKY, neither in L nor in D. In contrast, in SHR, the music of Mozart presented in L significantly decreased HR and left BP unaffected, leading to a small decrease in cardiac output. The music of Ligeti significantly increased BP both in L and in D and reflexively reduced HR in L, the effects being long-lasting over 24 h. Interestingly, white noise at 75 dB had no effect at all on either function in both strains. The effects of both Mozart and Ligeti cannot be attributed to a stress reaction, as stress due to cage switch increased HR and BP both in WKY and SHR. The study clearly demonstrates that music of different character (tempo, rhythm, pitch, tonality) can

Hormonal control of fat accumulation in L-glutamate-treated obese rats

International Nuclear Information System (INIS)

Remke, H.; Wilsdorf, A.; Mueller, F.

1988-01-01

Persistently decreased concentrations of the growth hormone and the tissue-nonepinephrine in connection with growth retardation and obesity were investigated concerning the effects on cells of epididymal adipose tissue in postnatally injured glutamate-treated rats using 14 C-labelled tracers. Diminished secretion of growth hormone causes in adipocytes increased glucose intake, amplification of the insulin effect, and fat accumulation. A supersensitivity towards norepinephrine in adipocytes in vitro is due to diminished concentration of this hormone in the tissue. Insulin resistance is developed at the beginning of the stationary phase of obesity in these animals. (author)

Increased atrial natriuretic factor receptor density in cultured vascular smooth muscle cells of the spontaneously hypertensive rat

International Nuclear Information System (INIS)

Khalil, F.; Fine, B.; Kuriyama, S.; Hatori, N.; Nakamura, A.; Nakamura, M.; Aviv, A.

1987-01-01

To explore the role of the atrial natriuretic factor (ANF) system in the pathophysiology of hypertension we examined the binding kinetics of synthetic ANF to cultured vascular smooth muscle cells (VSMCs) derived from the spontaneously hypertensive rat (SHR) and two normotensive controls-the Wistar Kyoto (WKY) and American Wistar (W). The number of maximal binding sites (Bmax) per cell (mean +/- SEM; X10(3] were: SHR = 278.0 +/- 33.0, WKY = 28.3 +/- 7.1 and W = 26.6 +/- 4.2. The differences between the SHR and normotensive strains were significant at p less than 0.001. The equilibrium dissociation constant (Kd; X 10(-9)M) was higher in SHR VSMCs (0.94 +/- 0.14) than in WKY (0.22 +/- 0.09; p less than 0.01) and W (0.39 +/- 0.14; p less than 0.02) cells. The plasma levels of the immunoreactive ANF were higher in SHR than the normotensive controls. We suggest that the relatively greater ANF receptor density in cultured VSMCs of the SHR represents a response to the in vitro environment which is relatively more deficient in ANF for VSMCs of the SHR as compared with the normotensive rats. Thus, the capacity of the SHR VSMC to regulate ANF receptor density appears to be independent of the blood pressure level

High-fat diet-induced plasma protein and liver changes in obese rats can be attenuated by melatonin supplementation.

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Wongchitrat, Prapimpun; Klosen, Paul; Pannengpetch, Supitcha; Kitidee, Kuntida; Govitrapong, Piyarat; Isarankura-Na-Ayudhya, Chartchalerm

2017-06-01

Obesity triggers changes in protein expression in various organs that might participate in the pathogenesis of obesity. Melatonin has been reported to prevent or attenuate such pathological protein changes in several chronic diseases. However, such melatonin effects on plasma proteins have not yet been studied in an obesity model. Using a proteomic approach, we investigated the effect of melatonin on plasma protein profiles after rats were fed a high-fat diet (HFD) to induce obesity. We hypothesized that melatonin would attenuate abnormal protein expression in obese rats. After 10weeks of the HFD, animals displayed increased body weight and fat accumulation as well as increased glucose levels, indicating an obesity-induced prediabetes mellitus-like state. Two-dimensional gel electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry revealed 12 proteins whose expression was altered in response to the HFD and the melatonin treatment. The altered proteins are related to the development of liver pathology, such as cirrhosis (α1-antiproteinase), thrombosis (fibrinogen, plasminogen), and inflammation (mannose-binding protein A, complement C4, complement factor B), contributing to liver steatosis or hepatic cell death. Melatonin treatment most probably reduced the severity of the HFD-induced obesity by reducing the amplitude of HFD-induced plasma protein changes. In conclusion, we identified several potential biomarkers associated with the progression of obesity and its complications, such as liver damage. Furthermore, our findings reveal melatonin's beneficial effect of attenuating plasma protein changes and liver pathogenesis in obese rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats

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Muhammad Tayyab Akhtar

2016-08-01

Full Text Available Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM. Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM. Proton Nuclear Magnetic Resonance (1H-NMR spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese–diabetic (obdb rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats.

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Amin, Kamal A; Nagy, Mohamed A

2009-10-16

Obesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity. To investigate the development of obesity in response to a high fat diet (HFD) and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF) (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice) on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats. White male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr), 30 rats fed a high-fat diet (HFD) for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD), the 2nd group HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10th week (start time for treatments) for 4 weeks.Body weight, lipid profile & renal function (urea, uric acid creatinine) ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB) the oxidative stress marker reduced glutathione (GSH), and Malondialdehyde (MDA) catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed. Data showed that feeding HFD diet significantly increased final body weight, triglycerides (TG), total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile.Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia, hyperinsulinemia, and high insulin resistance (IR

Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats

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Amin Kamal A

2009-10-01

Full Text Available Abstract Background Obesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity. Aim To investigate the development of obesity in response to a high fat diet (HFD and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats. Method White male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr, 30 rats fed a high-fat diet (HFD for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD, the 2nd group HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10th week (start time for treatments for 4 weeks. Body weight, lipid profile & renal function (urea, uric acid creatinine ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB the oxidative stress marker reduced glutathione (GSH, and Malondialdehyde (MDA catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed. Results Data showed that feeding HFD diet significantly increased final body weight, triglycerides (TG, total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile. Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia

Obesity improves myocardial ischaemic tolerance and RISK signalling in insulin-insensitive rats

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Daniel Donner

2013-03-01

Obesity with associated metabolic disturbances worsens ischaemic heart disease outcomes, and rodent studies confirm that obesity with insulin-resistance impairs myocardial resistance to ischemia-reperfusion (I-R injury. However, the effects of obesity per se are unclear, with some evidence for paradoxic cardioprotection (particularly in older subjects. We tested the impact of dietary obesity on I-R tolerance and reperfusion injury salvage kinase (RISK signalling in hearts from middle-aged (10 months old insulin-insensitive rats. Hearts from Wistar rats on either a 32-week control (CD or high carbohydrate obesogenic (OB diet were assessed for I-R resistance in vivo (45 minutes left anterior descending artery occlusion and 120 minutes reperfusion and ex vivo (25 minutes ischemia and 60 minutes reperfusion. Expression and δ-opioid receptor (δ-OR phospho-regulation of pro-survival (Akt/PKB, Erk1/2, eNOS and pro-injury (GSK3β enzymes were also examined. OB rats were heavier (764±25 versus 657±22 g for CD; P<0.05, hyperleptinaemic (11.1±0.7 versus 5.0±0.7 for CD; P<0.01 and comparably insulin-insensitive (HOMA-IR of 63.2±3.3 versus 63.2±1.6 for CD. In vivo infarction was more than halved in OB (20±3% versus CD rats (45±6% P<0.05, as was post-ischaemic lactate dehydrogenase efflux (0.4±0.3 mU/ml versus 5.6±0.5 mU/ml; P<0.02 and ex vivo contractile dysfunction (62±2% versus 44±6% recovery of ventricular force; P<0.05. OB hearts exhibited up to 60% higher Akt expression, with increased phosphorylation of eNOS (+100%, GSK3β (+45% and Erk1/2 (+15%. Pre-ischaemic δ-OR agonism with BW373U86 improved recoveries in CD hearts in association with phosphorylation of Akt (+40%, eNOS (+75% and GSK3β (+30%, yet failed to further enhance RISK-NOS activation or I-R outcomes in OB hearts. In summary, dietary obesity in the context of age-related insulin-insensitivity paradoxically improves myocardial I-R tolerance, in association with moderate hyperleptinaemic and

Potassium and calcium channel gene expression in small arteries in porcine and rat models of diet-induced obesity (Poster)

DEFF Research Database (Denmark)

Jensen, Lars Jørn; Salomonsson, Max; Sørensen, Charlotte Mehlin

2014-01-01

Obesity is an increasing problem worldwide leading to cardiovascular morbidity. Only limited information exists on the transcriptional regulation of arterial K+ and Ca2+ channels in obesity. We quantified, by real-time PCR, mRNA expression of K+ channels and L-type Ca2+ channels (LTCC) in small...... mesenteric (MA), middle cerebral (MCA), and left coronary arteries (LCA) of lean vs. obese rats and minipigs. Male Sprague Dawley rats were fed a high-fat (FAT; N=5), high-fructose (FRUC; N=7), high-fat/high-fructose (FAT/FRUC; N=7) or standard diet (STD; N=7-11) for 28 Weeks. FAT and FAT/FRUC became obese...... increased in OB and OB+DIAB. BKca, IKca, SKca and/or LTCC mRNA was up-regulated in LCA from OB and OB+DIAB (n.s.). Expression of BKca mRNA was increased, whereas IKca mRNA decreased in MCA from OB (n.s.). SKca mRNA was decreased in MA from OB (n.s.). Diet-induced obesity in rats and minipigs lead to complex...

Maternal obesity and post-natal high fat diet disrupt hepatic circadian rhythm in rat offspring

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Offspring of obese (Ob) rat dams gain greater body wt and fat mass when fed high-fat diet (HFD) as compared to controls. Alterations of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver. We sought to determine if maternal obesity (MOb) leads to p...

Effect of Herbal Acupuncture with Sang-hwang(Phellinus linteus on High Fat Diet-induced Obesity in Rats

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Ji Hyun Kim

2004-02-01

Full Text Available Acupuncture has fairly good weight-reducing effect in treating simple obesity due to the neuroendocrine regulation. In this study, the anti-obesity effects of herbal acupuncture (HA with Sang-hwang (Phellinus linteus at Fuai (SP16 were investigated in the rat fed on high-fat (HF diet. Sang-hwang mushroom has been proven to have anti-carcinogenic effects and Sang-hwang extracts are highly effective in treatment and preventive treatment of AIDS, diabetes and high blood-pressure. To determine whether the Sang-hwang herbal acupuncture may have the anti-obesity effect, male Sprague-Dawley (4-wk-old rats were fed a HF diet for 5 wk, which produced significant weight gain compared to rats were fed a normal diet, and then herbal acupuncture were treated for 3 wk in HF diet group. The body weight, food consumption, food effeciency ratio (FER, body fat mass, plasma nitric oxide (NO were investigated in rats fed on normal diet, HF diet, and HF diet with HA (HF-diet-HA groups. NO has been proposed to be involved in the regulation of food intake. In addition, the expression of appetite peptides such as orexigenic peptide neuropeptide Y (NPY and the anorectic peptide cholecystokinin (CCK were observed in the hypothalamus. HF-HA group reduced body weight gain, FER, body fat contents and NO concentration compared to HF diet group. The expression of NPY was reduced in arcuate nucleus (ARC, and CCK was increased in the paraventricular nucleus (PVN after treatment of HA. In conclusion, Sang-hwang HA reduced adipocity, plasma NO and hypothalamic NPY, but increased CCK expression in the HF diet-induced obesity rat, therefore HA may have anti-obesity action through regulating body weight and appetite peptide of the central nervous system.

Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar–Kyoto rats

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Kanintra Suwanmanon

2014-12-01

Full Text Available In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar–Kyoto (WKY rats were randomized into seven groups. Until the 8th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD; Group 2, medium dose of GABA and nattokinase in the SHR (SMD; Group 3, low dose of GABA and nattokinase in the SHR (SLD; Group 4, negative control in the SHR (SD; Group 5, positive control in the SHR (SM; Group 6, high dose of GABA and nattokinase in the WKY (WHD; and Group 7, negative control in the WKY (WD. Distilled water served as the negative control, and captopril (50 mg/kg, a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8th week to the 16th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity.

Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats.

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Suwanmanon, Kanintra; Hsieh, Pao-Chuan

2014-12-01

In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR) caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA) and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar-Kyoto (WKY) rats were randomized into seven groups. Until the 8 th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD); Group 2, medium dose of GABA and nattokinase in the SHR (SMD); Group 3, low dose of GABA and nattokinase in the SHR (SLD); Group 4, negative control in the SHR (SD); Group 5, positive control in the SHR (SM); Group 6, high dose of GABA and nattokinase in the WKY (WHD); and Group 7, negative control in the WKY (WD). Distilled water served as the negative control, and captopril (50 mg/kg), a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8 th week to the 16 th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity. Copyright © 2014. Published by Elsevier B.V.

Excessive endoplasmic reticulum stress and decreased neuroplasticity-associated proteins in prefrontal cortex of obese rats and the regulatory effects of aerobic exercise.

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Li, Feng; Liu, Bei Bei; Cai, Ming; Li, Jing Jing; Lou, Shu-Jie

2018-04-06

Studies have shown high fat diet induced obesity may cause cognition impairment and down-regulation of neuroplasticity-associated proteins, while aerobic exercise could improve that damage. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating neuroplasticity-associated proteins expression, folding and post-translational modification in hippocampus of obese rodent models, however, the effects of ERS on neuroplasticity-associated proteins and possible underlying mechanisms in prefrontal cortex are not fully clear. In order to clarify changes of neuroplasticity-associated proteins and ERS in the prefrontal cortex of obese rats, male SD rats were fed on high fat diet for 8 weeks to establish the obese model. Then, 8 weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that high fat diet induced obesity caused hyperlipidemia, and significantly promoted FATP1 expression in the prefrontal cortex, meanwhile, we found up-regulation of GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2, reflecting the activation of ERS and ERS-mediated apoptosis. Moreover, reduced BDNF and SYN was found in obese rats. However, FATP1, GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2 expressions were obviously reversed by aerobic exercise intervention. These results suggested that dietary obesity could induce Prefrontal ERS in SD rats and excessive ERS may play a critical role in decreasing the levels of neuroplasticity-associated proteins. Moreover, aerobic exercise could relieve ERS, thus promoted the expression of neuroplasticity-associated proteins. Copyright © 2018. Published by Elsevier Inc.

Upregulation of the dorsal raphe nucleus-prefrontal cortex serotonin system by chronic treatment with escitalopram in hyposerotonergic Wistar-Kyoto rats

NARCIS (Netherlands)

Yamada, Makiko; Kawahara, Yukie; Kaneko, Fumi; Kishikawa, Yuki; Sotogaku, Naoki; Poppinga, Wilfred J.; Folgering, Joost H. A.; Dremencov, Eliyahu; Kawahara, Hiroshi; Nishi, Akinori

Wistar-Kyoto (WKY) rats are sensitive to chronic stressors and exhibit depression-like behavior. Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons projecting to the prefrontal cortex (PFC) comprise the important neurocircuitry underlying the pathophysiology of depression. To evaluate the DRN-PFC

Protective Effects of Tamarillo (Cyphomandra betacea Extract against High Fat Diet Induced Obesity in Sprague-Dawley Rats

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Noor Atiqah Aizan Abdul Kadir

2015-01-01

Full Text Available This study aims to investigate the protective effect of Cyphomandra betacea in adult male Sprague-Dawley rats fed with high fat diet. Rats were fed on either normal chow or high fat diet for 10 weeks for obesity induction phase and subsequently received C. betacea extract at low dose (150 mg kg−1, medium dose (200 mg kg−1, or high dose (300 mg kg−1 or placebo via oral gavages for another 7 weeks for treatment phase. Treatment of obese rats with C. betacea extracts led to a significant decrease in total cholesterol and significant increase in HDL-C (p<0.05. Also there was a trend of positive reduction in blood glucose, triglyceride, and LDL-C with positive reduction of body weight detected in medium and high dosage of C. betacea extract. Interestingly, C. betacea treated rats showed positive improvement of superoxide dismutase (SOD activity and glutathione peroxidase (GPx activity along with a significant increase of total antioxidant status (TAS (p<0.05. Further, rats treated with C. betacea show significantly lower in TNF-α and IL-6 activities (p<0.05. This study demonstrates the potential use of Cyphomandra betacea extract for weight maintenance and complimentary therapy to suppress some obesity complication signs.

Grape Polyphenols Increase the Activity of HDL Enzymes in Old and Obese Rats

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Andriy L. Zagayko

2013-01-01

Full Text Available HDL particles are protein-rich particles that act as a vehicle for reverse cholesterol transport from tissues to the liver. The purpose of this study was to investigate age-dependent changes in the functional activity of HDL and the effect of high-energy diet on this index, as well as to correct it under the influence of grape polyphenols from “Enoant” obtained from Vitis vinifera grapes. We observed the age-dependent composition changes in HDL particle. It was shown that total lipids and triacylglycerol (TG levels were higher in 24-month-old animals. In obese rats, HDL total lipids and TG levels were higher in 24-month-old than in the 3-month-old and 12-month-old groups but did not differ from 24-month-old group. The plasma HDL paraoxonase (PON and lecithin:cholesterol acyltransferase (LCAT activity levels were decreased in old-aged rats, and cholesteryl ester transfer protein (CETP activity was higher in old rats. Keeping 12-month-old animals on high-fructose diet completely leveled the age differences in the data that have been measured between 12-month-old and 24-month-old rats. After “Enoant” administration, an increase of HDL PON and LCAT activity levels and a reduction of CETP activity were found in 24-month-old and obese rats.

Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning

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In utero exposure to maternal obesity increases the offspring’s risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND) 21. In the current s...

Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Leprfa Rat: A New Obese Type 2 Diabetic Model

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Yusuke Kemmochi

2013-01-01

Full Text Available Spontaneously Diabetic Torii Leprfa (SDT fatty rat, established by introducing the fa allele of the Zucker fatty rat into SDT rat genome, is a new model of obese type 2 diabetes. Both male and female SDT fatty rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT rats. With early incidence of diabetes mellitus, diabetic complications, such as nephropathy, retinopathy, and neuropathy, in SDT fatty rats were seen at younger ages compared to those in the SDT rats. In this paper, we overview pathophysiological features in SDT fatty rats and also describe new insights regarding the hematology, blood pressure, renal complications, and sexual dysfunction. The SDT fatty rats showed an increase of leukocytes, especially the monocyte count, prominent hypertension associated with salt drinking, end-stage renal disease with aging, and hypogonadism. Unlike other diabetic models, the characteristic of SDT fatty rat is to present an incidence of diabetes in females, hypertension, and retinopathy. SDT fatty rat is a useful model for analysis of various metabolic disorders and the evaluation of drugs related to metabolic disease.

ZINC-INDUCED HYPERLEPTINEMIA IN RATS RELATED TO THE AMELIORATION OF SUCROSE-INDUCED OBESITY WITH ZINC REPLETION

International Nuclear Information System (INIS)

HEIBASHY, M.I.; EL-NAHLA, A.M.; ASHOUR, I.; SALEH, SH.Y.A.

2008-01-01

Thirty adult albino rats (Rattus rattus) at 6 weeks of age were divided into three groups (ten for each). The first group was fed a standard laboratory diet for 8 weeks (control). The second group was made obese by giving them 32% sucrose solution in addition to the standard laboratory diet .The third group was received zinc supplementation (50 mg zinc acetate/ litre) with their sucrose solution. Body weight of all rats was measured weekly for 8 weeks. At 14 weeks of age, rats were killed and fasting blood samples were obtained. Serum glucose, insulin, cholesterol, triglyceride, leptin, tumour necrosis factor-α and zinc were measured.Results showed remarkable changes in body weights in sucrose fed rats only when compared to control and supplemented zinc rats group. Serum glucose, insulin, cholesterol and triglycerides were significantly increased in sucrose fed rats than both control and sucrose with zinc group. Serum leptin showed significant increase in sucrose fed rats than control and also showed higher significant value in sucrose fed rats supplemented with zinc comparing with sucrose fed rats and control ones. Tumour necrosis factor-? did not show any significant difference between all groups. Serum zinc concentration was decreased significantly in sucrose fed rats as compared to control. On the other hand, it was increased significantly in sucrose fed rats supplemented with zinc than other both groups. It could be concluded that zinc supplementation induced hyperleptinemia caused ameliorating effects in obese rats

Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

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Song, Xin-Ai; Jia, Lin-Lin [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Meng [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Yuan, Zu-Yi [Department of Cardiovascular Medicine, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Guo, Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Li, Hui-Hua [Key Laboratory of Remodeling-related Cardiovascular Diseases, Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Liu, Hao, E-mail: haoliu75@163.com [Department of Neurosurgery, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

2014-11-15

We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

High-fat-diet-induced obesity causes an inflammatory and tumor-promoting microenvironment in the rat kidney

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Kerstin Stemmer

2012-09-01

Obesity and concomitant comorbidities have emerged as public health problems of the first order. For instance, obese individuals have an increased risk for kidney cancer. However, direct mechanisms linking obesity with kidney cancer remain elusive. We hypothesized that diet-induced obesity (DIO promotes renal carcinogenesis by inducing an inflammatory and tumor-promoting microenvironment. We compared chow-fed lean Wistar rats with those that were sensitive (DIOsens or partially resistant (DIOres to DIO to investigate the impact of body adiposity versus dietary nutrient overload in the development of renal preneoplasia and activation of tumor-promoting signaling pathways. Our data clearly show a correlation between body adiposity, the severity of nephropathy, and the total number and incidence of preneoplastic renal lesions. However, similar plasma triglyceride, plasma free fatty acid and renal triglyceride levels were found in chow-fed, DIOres and DIOsens rats, suggesting that lipotoxicity is not a critical contributor to the renal pathology. Obesity-related nephropathy was further associated with regenerative cell proliferation, monocyte infiltration and higher renal expression of monocyte chemotactic protein-1 (MCP-1, interleukin (IL-6, IL-6 receptor and leptin receptor. Accordingly, we observed increased signal transducer and activator of transcription 3 (STAT3 and mammalian target of rapamycin (mTOR phosphorylation in tubules with preneoplastic phenotypes. In summary, our results demonstrate that high body adiposity induces an inflammatory and proliferative microenvironment in rat kidneys that promotes the development of preneoplastic lesions, potentially via activation of the STAT3 and mTOR signaling pathways.

Overfeeding-Induced Obesity in Rats : Insulin Sensitivity and Autonomic Regulation of Metabolism

NARCIS (Netherlands)

Balkan, B; Strubbe, J.H.; Bruggink, J.E.; Steffens, A.B.

1993-01-01

The metabolic consequences of the development of obesity and the underlying mechanisms were investigated. For this purpose, male rats were overfed for 5 weeks through long-term gastric catheters. Permanent cardiac cannulas implanted before the overfeeding period allowed frequent blood sampling and

Vitamin A as a key regulator of obesity & its associated disorders: Evidences from an obese rat model

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Shanmugam M Jeyakumar

2015-01-01

Full Text Available During the last century, vitamin A has evolved from its classical role as a fat-soluble vitamin and attained the status of para-/autocrine hormone. Besides its well-established role in embryogenesis, growth and development, reproduction and vision, vitamin A has also been implicated in several other physiological processes. Emerging experimental evidences emphasize adipose tissue as an active endocrine organ with great propensity to continuous growth (throughout life. Due to various genetic and lifestyle factors, excess energy accumulates in adipose tissue as fat, resulting in obesity and other complications such as type 2 diabetes, hypertension, and cardiovascular disease. Recent in vitro and in vivo studies have shed light on vitamin A metabolites; retinaldehyde and retinoic acid and participation of their pathway proteins in the regulation of adipose tissue metabolism and thus, obesity. In this context, we discuss here some of our important findings, which establish the role of vitamin A (supplementation in obesity and its associated disorders by employing an obese rat model; WNIN/Ob strain.

Opuntia ficus indica (nopal) attenuates hepatic steatosis and oxidative stress in obese Zucker (fa/fa) rats.

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Morán-Ramos, Sofía; Avila-Nava, Azalia; Tovar, Armando R; Pedraza-Chaverri, José; López-Romero, Patricia; Torres, Nimbe

2012-11-01

Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as obesity, insulin resistance, and oxidative stress. Nopal, a cactus plant widely consumed in the Mexican diet, is considered a functional food because of its antioxidant activity and ability to improve biomarkers of metabolic syndrome. The aim of this study was to assess the effect of nopal consumption on the development of hepatic steatosis and hepatic oxidative stress and on the regulation of genes involved in hepatic lipid metabolism. Obese Zucker (fa/fa) rats were fed a control diet or a diet containing 4% nopal for 7 wk. Rats fed the nopal-containing diet had ∼50% lower hepatic TG than the control group as well as a reduction in hepatomegaly and biomarkers of hepatocyte injury such as alanine and aspartate aminotransferases. Attenuation of hepatic steatosis by nopal consumption was accompanied by a higher serum concentration of adiponectin and a greater abundance of mRNA for genes involved in lipid oxidation and lipid export and production of carnitine palmitoyltransferase-1 and microsomal TG transfer proteins in liver. Hepatic reactive oxygen species and lipid peroxidation biomarkers were significantly lower in rats fed nopal compared with the control rats. Furthermore, rats fed the nopal diet had a lower postprandial serum insulin concentration and a greater liver phosphorylated protein kinase B (pAKT):AKT ratio in the postprandial state. This study suggests that nopal consumption attenuates hepatic steatosis by increasing fatty acid oxidation and VLDL synthesis, decreasing oxidative stress, and improving liver insulin signaling in obese Zucker (fa/fa) rats.

Acute insulin-induced elevations of circulating leptin and feeding inhibition in lean but not obese rats.

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Singh, Kimberly A; Boozer, Carol N; Vasselli, Joseph R

2005-08-01

Insulin has been shown to stimulate leptin mRNA expression acutely in rat adipose tissue, but its short-term effects on circulating leptin levels, and subsequent feeding behavior, have not been well described. We used 11-mo-old female selectively bred obesity-resistant (OR) and obesity-prone (OP) Sprague-Dawley rats maintained on laboratory chow to investigate this question. At testing, body weights and basal leptin levels of the OP rats were significantly elevated compared with the OR rats. In the 3-h fasted state, injection of 2.0 U insulin/kg ip resulted in significant elevations of plasma leptin at 4 h postinjection in both OP and OR groups (hour 4, +2.50 and +5.98 ng/ml, respectively). In separate feeding tests with the same groups, intake of laboratory chow pellets was significantly inhibited during hours 2-4 after 2.0 U/kg of insulin in the OR (-80.1%, P < 0.05), but not in the OP group, compared with intake after saline injections. In feeding tests with palatable moderately high-fat pellets after 2.0 and 3.0 U insulin/kg ip, significant decreases between hours 2 and 4 in intake were seen in the OR group only (-41.0 and -68.3%, respectively). Thus feeding inhibition coincides with insulin-induced elevations of plasma leptin in lean but not obese Sprague-Dawley rats. Our data suggest that elevations of leptin within the physiological range may contribute to short-term inhibition of food intake in rats and that this process may be stimulated by feeding-related insulin release.

EFFECTS OF PHYSICAL EXERCISES ON TRIACYLGLYCEROL LEVEL IN SKELETAL MUSCLES IN DIETARY-INDUCED OBESE RATS

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I. Yu. Yakimovich

2014-01-01

Full Text Available The accumulation of triacylglycerol in peripheral tissues is one of mechanisms of insulin resistance. This paper presents the investigation of the influence of aerobic and anaerobic physical exercises on triacylglycerol level in skeletal muscles and on insulin resistance in dietary-induced obese rats. It is estimated that a high-energy (HE diet causes the accumulation of triacylglycerols in skeletal muscles that leads to high resistance to insulin. Aerobic and anaerobic physical exercises reduce the level of triacylglycerols in skeletal  muscles  and  raise  sensitivity to  insulin  in  obese  rats.  Physical  exercises  raise  the  level  of triacylglycerols in skeletal muscles in standard-diet rats that probably is the adaptation to high energy expenditure, but does not lead to high insulin resistance.

Changes in gut microbiota in rats fed a high fat diet correlate with obesity-associated metabolic parameters.

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Lecomte, Virginie; Kaakoush, Nadeem O; Maloney, Christopher A; Raipuria, Mukesh; Huinao, Karina D; Mitchell, Hazel M; Morris, Margaret J

2015-01-01

The gut microbiota is emerging as a new factor in the development of obesity. Many studies have described changes in microbiota composition in response to obesity and high fat diet (HFD) at the phylum level. In this study we used 16s RNA high throughput sequencing on faecal samples from rats chronically fed HFD or control chow (n = 10 per group, 16 weeks) to investigate changes in gut microbiota composition at the species level. 53.17% dissimilarity between groups was observed at the species level. Lactobacillus intestinalis dominated the microbiota in rats under the chow diet. However this species was considerably less abundant in rats fed HFD (Pdevelopment of the obese phenotype, we correlated their abundance with metabolic parameters associated with obesity. Of the taxa contributing the most to dissimilarity between groups, 10 presented significant correlations with at least one of the tested parameters, three of them correlated positively with all metabolic parameters: Phascolarctobacterium, Proteus mirabilis and Veillonellaceae, all propionate/acetate producers. Lactobacillus intestinalis was the only species whose abundance was negatively correlated with change in body weight and fat mass. This species decreased drastically in response to HFD, favouring propionate/acetate producing bacterial species whose abundance was strongly correlated with adiposity and deterioration of metabolic factors. Our observations suggest that these species may play a key role in the development of obesity in response to a HFD.

Blockade of RAGE in Zucker obese rats with experimental periodontitis

DEFF Research Database (Denmark)

Grauballe, M B; Østergaard, J A; Schou, S

2017-01-01

BACKGROUND AND OBJECTIVE: Periodontitis and type 2 diabetes mellitus (T2D) are two interrelated chronic diseases. Periodontitis is more prevalent in patients with T2D than in healthy subjects, and studies indicate that periodontitis impacts the metabolic control of patients with T2D. Hyperglycemia...... on the interrelationship between periodontitis and T2D in a rat model of both diseases. MATERIAL AND METHODS: Zucker obese rats (HsdHlr:ZUCKER-Lepr (fa/fa) ) and their lean littermates were divided into five treatment groups, with and without periodontitis. Monoclonal anti-RAGE IgG3 were injected into the rats three times...... evaluated in plasma. Kidney complications were evaluated by quantitative real-time PCR, the creatinine clearance rate, the albumin excretion rate and kidney hypertrophy. Periodontitis was evaluated by morphometric registration of alveolar bone loss and radiographic recording of bone support. RESULTS...

Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats

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Ayyalasomayajula Vajreswari

2011-06-01

Full Text Available Abstract Background 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and its inhibition ameliorates obesity and metabolic syndrome. So far, no studies have reported the effect of dietary vitamin A on 11β-HSD1 activity in visceral fat and liver under normal and obese conditions. Here, we studied the effect of chronic feeding of vitamin A-enriched diet (129 mg/kg diet on 11β-HSD1 activity in liver and visceral fat of WNIN/Ob lean and obese rats. Methods Male, 5-month-old, lean and obese rats of WNIN/Ob strain (n = 16 for each phenotype were divided into two subgroups consisting of 8 rats of each phenotype. Control groups received stock diet containing 2.6 mg vitamin A/kg diet, where as experimental groups received diet containing 129 mg vitamin A/Kg diet for 20 weeks. Food and water were provided ad libitum. At the end of the experiment, tissues were collected and 11β-HSD1 activity was assayed in liver and visceral fat. Results Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα, the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα, a nuclear transcription factor which is known to downregulate 11β-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes. Conclusions This study suggests that chronic consumption of vitamin A-enriched diet decreases 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa.

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Abdelali Agouni

Full Text Available BACKGROUND: Obesity is associated with increased risks for development of cardiovascular diseases. Epidemiological studies report an inverse association between dietary flavonoid consumption and mortality from cardiovascular diseases. We studied the potential beneficial effects of dietary supplementation of red wine polyphenol extract, Provinols, on obesity-associated alterations with respect to metabolic disturbances and cardiovascular functions in Zucker fatty (ZF rats. METHODOLOGY/PRINCIPAL FINDINGS: ZF rats or their lean littermates received normal diet or supplemented with Provinols for 8 weeks. Provinols improved glucose metabolism by reducing plasma glucose and fructosamine in ZF rats. Moreover, it reduced circulating triglycerides and total cholesterol as well as LDL-cholesterol in ZF rats. Echocardiography measurements demonstrated that Provinols improved cardiac performance as evidenced by an increase in left ventricular fractional shortening and cardiac output associated with decreased peripheral arterial resistances in ZF rats. Regarding vascular function, Provinols corrected endothelial dysfunction in aortas from ZF rats by improving endothelium-dependent relaxation in response to acetylcholine (Ach. Provinols enhanced NO bioavailability resulting from increased nitric oxide (NO production through enhanced endothelial NO-synthase (eNOS activity and reduced superoxide anion release via decreased expression of NADPH oxidase membrane sub-unit, Nox-1. In small mesenteric arteries, although Provinols did not affect the endothelium-dependent response to Ach; it enhanced the endothelial-derived hyperpolarizing factor component of the response. CONCLUSIONS/SIGNIFICANCE: Use of red wine polyphenols may be a potential mechanism for prevention of cardiovascular and metabolic alterations associated with obesity.

Tubulo-glomerular feedback response: enhancement in adult spontaneously hypertensive rats and effects of anaesthetics

DEFF Research Database (Denmark)

Leyssac, P P; Holstein-Rathlou, N H

1989-01-01

. Maximum TGF pressure response was 28.6% greater in SHR than in the normotensive rats (13.3 vs. 9.5 mm Hg; p less than 0.025). The sensitivity, as estimated from the slope of the feedback curve at the Tp [f'(Tp)] was 87% greater in SHR than in WKY. There was no significant difference between...

Evaluation of the Ca2+ distribution in aortic tissue of spontaneously hypertensive and normotensive rats

International Nuclear Information System (INIS)

Spieker, C.; Zidek, W.; von Bassewitz, D.B.; Heck, D.; Rahn, K.H.

1991-01-01

In the present study, particle-induced X-ray emission (PIXE) was used to get information on the spatial distribution of Ca 2+ in aortas of spontaneously hypertensive rats (SHR) and normotensive controls aged 1 week, 4 weeks, and 12 weeks. To differentiate changes in Ca 2+ metabolism in hypertensive arteries from secondary phenomena due to the arteriosclerosis, the animals were examined in the earliest stage of hypertension. It was found that the Ca 2+ content was not elevated in the aortic smooth muscle of SHR aged 1 week (n = 11), as compared to normotensive controls (n = 10) (186.8 +/- 89.9 micrograms Ca 2+ /g tissue v 254.0 +/- 173.3 micrograms Ca 2+ /g). The Ca 2+ content was raised (P less than .05) in the aortic smooth muscle of SHR aged 4 weeks (n = 13), as compared to 12 WKY rats (4 weeks) (726.0 +/- 130.4 micrograms Ca 2+ /g tissue v 440.3 +/- 214.4 micrograms Ca 2+ /g) and in 17 SHR (3 months), as compared to 13 WKY rats, respectively (3390.1 +/- 729.9 micrograms Ca 2+ /g tissue v 1632.1 +/- 569.5 micrograms Ca 2+ /g). The results confirm the age-related increase in the arterial Ca 2+ content in normotensive rats and demonstrate additionally that this age-related rise in arterial Ca 2+ content is accelerated in SHR

Physical exercise restores microvascular function in obese rats with metabolic syndrome.

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Machado, Marcus Vinicius; Vieira, Aline Bomfim; Nascimento, Alessandro Rodrigues; Martins, Rômulo Lanza; Daleprane, Julio Beltrame; Lessa, Marcos Adriano; Tibiriçá, Eduardo

2014-11-01

Obesity and metabolic syndrome are related to systemic functional microvascular alterations, including a significant reduction in microvessel density. The aim of this study was to investigate the effects of exercise training on functional capillary density in the skeletal muscle and skin of obese rats with metabolic syndrome. We used male Wistar-Kyoto rats that had been fed a standard commercial diet (CON) or high-fat diet (HFD) for 32 weeks. Animals receiving the HFD were randomly divided into sedentary (HFD+SED) and training groups (HFD+TR) at the 20(th) week. After 12 weeks of aerobic treadmill training, the maximal oxygen uptake (VO2max); hemodynamic, biochemical, and anthropometric parameters; and functional capillary density were assessed. In addition, a maximal exercise test was performed. Exercise training increased the VO2max (69 ± 3 mL/kg per min) and exercise tolerance (30 ± 1 min) compared with the HFD+SED (41 ± 6 mL/kg per min, P Exercise training also increased the number of spontaneously perfused capillaries in the skeletal muscle (252 ± 9 vs. 207 ± 9 capillaries/mm(2)) of the training group compared with that in the sedentary animals (260 ± 15 capillaries/mm(2)). These results demonstrate that exercise training reverses capillary rarefaction in our experimental model of metabolic syndrome and obesity.

Effects and mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats.

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Liu, Chih-Wei; Tsai, Hung-Cheng; Huang, Chia-Chang; Tsai, Chang-Youh; Su, Yen-Bo; Lin, Ming-Wei; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Li, Tzu-Hao; Huang, Shiang-Fen; Yang, Ying-Ying; Hou, Ming-Chih; Lin, Han-Chieh; Lee, Fa-Yauh; Lee, Shou-Dong

2018-05-01

In obesity, there are no effective therapies for parallel immune and metabolic abnormalities, including systemic/tissue insulin-resistance/inflammation, adiposity and hepatic steatosis. Caffeine has anti-inflammation, antihepatic steatosis, and anti-insulin resistance effects. In this study, we evaluated the effects and molecular mechanisms of 6 wk of caffeine treatment (HFD-caf) on immunological and metabolic abnormalities of high-fat diet (HFD)-induced obese rats. Compared with HFD vehicle (HFD-V) rats, in HFD-caf rats the suppressed circulating immune cell inflammatory [TNFα, MCP-1, IL-6, intercellular adhesion molecule 1 (ICAM-1), and nitrite] profiles were accompanied by decreased liver, white adipose tissue (WAT), and muscle macrophages and their intracellular cytokine levels. Metabolically, the increase in metabolic rates reduced lipid accumulation in various tissues, resulting in reduced adiposity, lower fat mass, decreased body weight, amelioration of hepatic steatosis, and improved systemic/muscle insulin resistance. Further mechanistic approaches revealed an upregulation of tissue lipogenic [(SREBP1c, fatty acid synthase, acetyl-CoA carboxylase)/insulin-sensitizing (GLUT4 and p-IRS1)] markers in HFD-caf rats. Significantly, ex vivo experiments revealed that the cytokine release by the cocultured peripheral blood mononuclear cell (monocyte) and WAT (adipocyte), which are known to stimulate macrophage migration and hepatocyte lipogenesis, were lower in HFD-V groups than HFD-caf groups. Caffeine treatment simultaneously ameliorates immune and metabolic pathogenic signals present in tissue to normalize immunolgical and metabolic abnormalities found in HFD-induced obese rats.

Effects of exercise and diet change on cognition function and synaptic plasticity in high fat diet induced obese rats

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2013-01-01

Background Nutritional imbalance-induced obesity causes a variety of diseases and in particular is an important cause of cognitive function decline. This study was performed on Sprague Dawley (SD) rats with 13-weeks of high fat diet-induced obesity in connection to the effects of regular exercise and dietary control for 8 weeks on the synaptic plasticity and cognitive abilities of brain. Methods Four weeks-old SD rats were adopted classified into normal-normal diet-sedentary (NNS, n = 8), obesity-high fat diet-sedentary (OHS, n = 8), obesity-high fat diet-training (OHT, n = 8), obesity-normal diet-sedentary (ONS, n = 8) and obesity- normal diet-training (ONT, n = 8). The exercise program consisted of a treadmill exercise administered at a speed of 8 m/min for 1–4 weeks, and 14 m/min for 5–8 weeks. The Western blot method was used to measure the expression of NGF, BDNF, p38MAPK and p-p38MAPK proteins in hippocampus of the brain, and expressions of NGF, BDNF, TrkA, TrkB, CREB and synapsin1 mRNA were analyzed through qRT-PCR. Results The results suggest cognitive function-related protein levels and mRNA expression to be significantly decreased in the hippocampus of obese rats, and synaptic plasticity as well as cognitive function signaling sub-pathway factors were also significantly decreased. In addition, 8-weeks exercises and treatment by dietary change had induced significant increase of cognitive function-related protein levels and mRNA expression as well as synaptic plasticity and cognitive function signaling sub-pathway factors in obese rats. In particular, the combined treatment had presented even more positive effect. Conclusions Therefore, it was determined that the high fat diet-induced obesity decreases plasticity and cognitive function of the brain, but was identified as being improved by exercises and dietary changes. In particular, it is considered that regular exercise has positive effects on memory span and learning

Angiotensin II Type 2 Receptor and Receptor Mas Are Colocalized and Functionally Interdependent in Obese Zucker Rat Kidney

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Patel, Sanket N; Ali, Quaisar; Samuel, Preethi

2017-01-01

The actions of angiotensin II type 2 receptor (AT2R) and the receptor Mas (MasR) are complex but show similar pronatriuretic function; particularly, AT2R expression and natriuretic function are enhanced in obese/diabetic rat kidney. In light of some reports suggesting a potential positive...... interaction between these receptors, we tested hypothesis that renal AT2R and MasR physically interact and are interdependent to stimulate cell signaling and promote natriuresis in obese rats. We found that infusion of AT2R agonist C21 in obese Zucker rats (OZR) increased urine flow and urinary Na excretion...... coimmunoprecipitated with MasR in cortical homogenate of OZR. Immunoblotting of cortical homogenate cross-linked with zero-length oxidative (sulfhydryl groups) cross-linker cupric-phenanthroline revealed a shift of AT2R and MasR bands upward with overlapping migration for their complexes which were sensitive...

Prostatic relaxation induced by agmatine is decreased in spontaneously hypertensive rats.

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Lee, Liang-Ming; Tsai, Tsung-Chin; Chung, Hsien-Hui; Tong, Yat-Ching; Cheng, Juei-Tang

2012-09-01

What's known on the subject? and What does the study add? Neurotransmitters are known to control prostate contractility. Agmatine is one of them and induces relaxation through imidazoline receptors. The paper shows that the action of agmatine is reduced in hypertensive rats, and that this change is related to the decrease of ATP-sensitive potassium channels in the prostate. The findings can increase our understanding of the possible underlying mechanism for the development of clinical benign prostatic hyperplasia. To compare agmatine-induced prostatic relaxation in hypertensive and control rats. To investigate the responsible mechanism(s) and the role of the ATP-sensitive potassium channel. Prostate strips were isolated from male spontaneously hypertensive (SH) rats and normal Wistar-Kyoto (WKY) rats for measurement of isometric tension. The strips were precontracted with 1 µmol/L phenylephrine or 50 mmol/L KCl. Dose-dependent relaxation of the prostatic strips was studied by cumulative administration of agmatine, 1 to 100 µmol/L, into the organ bath. Effects of specific antagonists on agmatine-induced relaxation were studied. Western blotting analysis was used to measure the gene expression of the ATP-sensitive potassium channel in the rat prostate. Prostatic relaxation induced by agmatine was markedly reduced in SH rats compared with WKY rats. The relaxation caused by agmatine was abolished by BU224, a selective imidazoline I(2)-receptor antagonist, but was not modified by efaroxan at a dose sufficient to block imidazoline I(1)-receptors. The relaxation induced by diazoxide at a concentration sufficient to activate ATP-sensitive potassium channels was markedly reduced in the SH rat prostate. Expressions of ATP-sensitive potassium channel sulphonylurea receptor and inwardly rectifying potassium channel (Kir) 6.2 subunits were both decreased in the prostate of SH rats. The decrease of agmatine-induced prostatic relaxation in SH rats is related to the change in

Metabolic Signatures of Kidney Yang Deficiency Syndrome and Protective Effects of Two Herbal Extracts in Rats Using GC/TOF MS

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Linjing Zhao

2013-01-01

Full Text Available Kidney Yang Deficiency Syndrome (KDS-Yang, a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrometry. WKY1, a polysaccharide extract from Astragalus membranaceus and Lycium barbarum, and WKY2, an aqueous extract from a similar formula containing Astragalus membranaceus, Lycium barbarum, Morinda officinalis, Taraxacum mongolicum, and Cinnamomum cassia presl, were used separately for protective treatments of KDS-Yang. The changes of serum metabolic profiles indicated that significant alterations of key metabolic pathways in response to abrupt hydrocortisone perturbation, including decreased energy metabolism (lactic acid, acetylcarnitine, lipid metabolism (free fatty acids, 1-monolinoleoylglycerol, and cholesterol, gut microbiota metabolism (indole-3-propionic acid, biosynthesis of catecholamine (norepinephrine, and elevated alanine metabolism, were attenuated or normalized with different degrees by the pretreatment of WKY1 or WKY2, which is consistent with the observations in which the two herbal agents could ameliorate biochemical markers of serum cortisone, adrenocorticotropic (ACTH, and urine 17-hydroxycorticosteroids (17-OHCS.

Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats.

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Ennequin, Gaël; Boisseau, Nathalie; Caillaud, Kevin; Chavanelle, Vivien; Gerbaix, Maude; Metz, Lore; Etienne, Monique; Walrand, Stéphane; Masgrau, Aurélie; Guillet, Christelle; Courteix, Daniel; Niu, Airu; Li, Yi-Ping; Capel, Fréderic; Sirvent, Pascal

2015-06-15

Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents. Here we assessed whether unbalanced diet is associated with alterations of the NRG1 signalling pathway and whether exercise and diet might restore NRG1 signalling in skeletal muscle of obese rats. We show that diet-induced obesity does not impair NRG1 signalling in rat skeletal muscle. We also report that endurance training and a well-balanced diet activate the NRG1 signalling in skeletal muscle of obese rats, possibly via a new mechanism mediated by the protease ADAM17. These results suggest that some beneficial effects of physical activity and diet in obese rats could be partly explained by stimulation of the NRG1 signalling pathway. Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was

Growth hormone and IGF-1 deficiency exacerbate high-fat diet-induced endothelial impairment in obese Lewis dwarf rats: implications for vascular aging.

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Bailey-Downs, Lora C; Sosnowska, Danuta; Toth, Peter; Mitschelen, Matthew; Gautam, Tripti; Henthorn, Jim C; Ballabh, Praveen; Koller, Akos; Farley, Julie A; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2012-06-01

Previous studies suggest that the age-related decline in circulating growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels significantly contribute to vascular dysfunction in aging by impairing cellular oxidative stress resistance pathways. Obesity in elderly individuals is increasing at alarming rates, and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging, GH/IGF-1 deficiency, and obesity interact to promote the development of cardiovascular disease remain unclear. To test the hypothesis that low circulating GH/IGF-1 levels exacerbate the pro-oxidant and proinflammatory vascular effects of obesity, GH/IGF-1-deficient Lewis dwarf rats and heterozygous control rats were fed either a standard diet or a high-fat diet (HFD) for 7 months. Feeding an HFD resulted in similar relative weight gains and increases in body fat content in Lewis dwarf rats and control rats. HFD-fed Lewis dwarf rats exhibited a relative increase in blood glucose levels, lower insulin, and impaired glucose tolerance as compared with HFD-fed control rats. Analysis of serum cytokine expression signatures indicated that chronic GH/IGF-1 deficiency exacerbates HFD-induced inflammation. GH/IGF-1 deficiency also exacerbated HFD-induced endothelial dysfunction, oxidative stress, and expression of inflammatory markers (tumor necrosis factor-α, ICAM-1) in aortas of Lewis dwarf rats. Overall, our results are consistent with the available clinical and experimental evidence suggesting that GH/IGF-1 deficiency renders the cardiovascular system more vulnerable to the deleterious effects of obesity.

Antiobesity Effect of Codonopsis lanceolata in High-Calorie/High-Fat-Diet-Induced Obese Rats

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Hye-Kyung Choi

2013-01-01

Full Text Available The antiobesity effects of Codonopsis lanceolata (CL were evaluated in a high-calorie/high-fat-diet (HFD- induced obesity rat model and 3T3-L1 cells. The Sprague-Dawley male rats were fed a normal diet (ND or a HFD for a period of 12 weeks. The rats were subdivided into groups: ND, ND + wild Codonopsis lanceolata (wCL (900 mg/kg/day, p.o., ND + cultivated Codonopsis lanceolata (cCL (900 mg/kg/day, p.o., HFD, HFD + wCL (100, 300, or 900 mg/kg/day, p.o., HFD + cCL (100, 300, or 900 mg/kg/day, p.o., and HFD + sibutramine. The body weight gains of the administered HFD + CL (wCL or CCL were lower than those of the rats fed with only the HFD group. Moreover, the weight of adipose pads and the serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol in the group administered HDL + CL were significantly lower than in the HFD group. The inhibitory effect of lipid accumulation in 3T3-L1 cells was measured by Oil Red O staining and reverse transcription-polymerase chain reaction (RT-PCR. Treatment of 3T3-L1 cells with wCL inhibited lipid accumulation and expression of C/EBPα and PPARγ. These results suggest that CL has a great potential as a functional food with anti-obesity effects and as a therapeutic alternative in the treatment of obesity.

The effects of altitude training on the AMPK-related glucose transport pathway in the red skeletal muscle of both lean and obese Zucker rats.

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Chen, Yu-Ching; Lee, Shin-Da; Kuo, Cha-Hua; Ho, Low-Tone

2011-01-01

The skeletal muscle AMP-activated protein kinase (AMPK)-related glucose transport pathway is involved in glucose homeostasis. In this study, we examined whether obese control Zucker rats had abnormal expression of proteins in the LKB1-AMPK-AS160-GLUT4 pathway in red gastrocnemius muscle compared to that in lean (normal) control Zucker rats. We also compared the chronic training effects of exercise, hypoxia, and altitude training on this pathway in lean and obese rats. At sea level, lean and obese rats were divided into 4 groups for 6 weeks training as follows: 1) control; 2) exercise (progressive daily swimming-exercise training with comparable exercise signals between the two groups); 3) hypoxia (8 hours of daily 14% O2 exposure); and 4) exercise plus hypoxia (also called altitude training). Seven animals were used for each group. The obese rats in the control group had higher body weights, elevated fasting insulin and glucose levels, and higher baseline levels of muscle AMPK and AS160 phosphorylation compared with those of lean control rats. For obese Zucker rats in the exercise or hypoxia groups, the muscle AMPK phosphorylation level was significantly decreased compared with that of the control group. For obese Zucker rats in the altitude training group, the levels of AMPK, AS160 phosphorylation, fasting insulin, and fasting glucose were decreased concomitant with an approximate 50% increase in the muscle GLUT4 protein level compared with those of the control group. In lean rats, the altitude training efficiently lowered fasting glucose and insulin levels and increased muscle AMPK and AS160 phosphorylation as well as GLUT4 protein levels. Our results provide evidence that long-term altitude training may be a potentially effective nonpharmacological strategy for treating and preventing insulin resistance based on its effects on the skeletal muscle AMPK-AS160-GLUT4 pathway.

Chronic type 1 diabetes in spontaneously hypertensive rats leads to exacerbated cardiac fibrosis.

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Black, Mary Jane; D'Amore, Angelo; Auden, Alana; Stamp, Laura; Osicka, Tanya; Panagiotopoulos, Sianna; Jerums, George

2010-01-01

Diabetes in human subjects is often associated with hypertension. The aim of this study was to examine the development of cardiac fibrosis following induction of type 1 diabetes in genetically hypertensive rats. Diabetes was induced by streptozotocin (STZ) injection in 8-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) for a duration of 16 or 24 weeks. Aged-matched, nondiabetic WKY and SHRs were used as controls. At termination of treatment, the rats were anaesthetized, hearts arrested in diastole and perfusion fixed. A comprehensive examination of cardiac fibrosis throughout the right and left ventricles was undertaken in picrosirius red-stained sections, using image analysis and by undertaking collagen type I and type III immunohistochemistry. Induction of diabetes in the SHRs led to a marked increase in the levels of interstitial fibrosis in the left ventricle plus septum (LV+S) at both 16 and 24 weeks duration (59% and 43% increase, respectively) and also in the right ventricle after 24 weeks duration of diabetes (35% increase compared to the nondiabetic SHR). Exacerbated perivascular fibrosis was also observed in the LV+S in the diabetic-hypertensive rats at the later time point. These effects of induction of diabetes were not observed in the normotensive strain. Our findings clearly demonstrate elevations in cardiac fibrosis when type 1 diabetes is combined with hypertension. Our findings thus stress the importance of closely monitoring both blood pressure and glucose levels in type 1 diabetic patients in order to prevent myocardial collagen deposition. Copyright © 2010 Elsevier Inc. All rights reserved.

Stroke Status Evoked Adhesion Molecule Genetic Alterations in Astrocytes Isolated from Stroke-Prone Spontaneously Hypertensive Rats and the Apigenin Inhibition of Their Expression

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Kazuo Yamagata

2010-01-01

Full Text Available We examined the possibility that the expression of adhesion molecules is regulated differently in cultured astrocytes from stroke-prone spontaneously hypertensive rats (SHRSP/IZM rats than in those from Wistar Kyoto rats (WKY/IZM by tumor necrosis factor-alpha (TNF- or hypoxia and reoxygenation (H/R and the inhibitory effects of apigenin. It was found that the expression of vascular cell adhesion molecule-1 (VCAM-1 by TNF- in astrocytes isolated from SHRSP/IZM was increased compared with that in WKY/IZM. The expression of monocyte chemotactic protein-1 (MCP-1 mRNA induced by H/R in SHRSP/IZM astrocytes was increased compared with that in normal oxygen concentrations. Apigenin strongly attenuated TNF--induced VCAM-1 mRNA and protein expression and suppressed the adhesion of U937 cells and SHRSP/IZM astrocytes. These results suggest that the expression levels of adhesion molecules during H/R affect disease outcome and can drive SHRSP/IZM to stroke. It is suggested that apigenin regulates adhesion molecule expression in reactive astrocytes during ischemia.

1,25 (OH)2 vitamin D3-induced 45Ca uptake in vascular myocytes cultured from spontaneously hypertensive and normotensive rats

International Nuclear Information System (INIS)

Xue, Hong; McCarron, D.A.; Bukoski, R.D.

1991-01-01

The effect of 1,25 (OH) 2 vitamin D 3 on basal 45 Ca uptake was examined in vasvular smooth muscle cells cultured from mesenteric arteries of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) normotensive rats. Basal uptake of 45 Ca was significantly greater in myocytes of WKY than SHR at 5, 10, 30 and 60 min incubation with the isotope. Incubation with 1 ng/ml 1,25 (OH) 2 vitamin D 3 for 48 hr increased basal 45 Ca uptake between 1-10 min in SHR and between 5-10 min in WKY. The dose-response relationship indicated that cells from both strains are equally sensitive to the calciotropic effects of 1,25 (OH) 2 vitamin D 3 with half-maximal stimulation occurring at approximately 0.3-0.4 ng/ml. In cells of both strains maximal stimulation of 45 Ca uptake was achieved only after a 12-24 hr period of incubation with hormone and pretreatment with cycloheximide inhibited 1,24 (OH) 2 vitamin D 3 -enhanced 45 Ca uptake. Although 45 Ca binding by extracellular matrix material was significantly greater in WKY than SHR, 1,25 (OH) 2 vitamin D 3 had no effect on the amount of matrix 45 Ca binding in either strain

Inhibition of Extracellular Signal-Regulated Kinases Ameliorates Hypertension-Induced Renal Vascular Remodeling in Rat Models

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Li Jing

2011-11-01

Full Text Available The aim of this study is to investigate the effect of the extracellular signal-regulated kinases 1/2 (ERK1/2 inhibitor, PD98059, on high blood pressure and related vascular changes. Blood pressure was recorded, thicknesses of renal small artery walls were measured and ERK1/2 immunoreactivity and erk2 mRNA in renal vascular smooth muscle cells (VSMCs and endothelial cells were detected by immunohistochemistry and in situ hybridization in normotensive wistar kyoto (WKY rats, spontaneously hypertensive rats (SHR and PD98059-treated SHR. Compared with normo-tensive WKY rats, SHR developed hypertension at 8 weeks of age, thickened renal small artery wall and asymmetric arrangement of VSMCs at 16 and 24 weeks of age. Phospho-ERK1/2 immunoreactivity and erk2 mRNA expression levels were increased in VSMCs and endothelial cells of the renal small arteries in the SHR. Treating SHR with PD98059 reduced the spontaneous hypertension-induced vascular wall thickening. This effect was associated with suppressions of erk2 mRNA expression and ERK1/2 phosphorylation in VSMCs and endothelial cells of the renal small arteries. It is concluded that inhibition of ERK1/2 ameliorates hypertension induced vascular remodeling in renal small arteries.

Effects of high-fat diet and fructose-rich diet on obesity, dyslipidemia and hyperglycemia in the WBN/Kob-Leprfa rat, a new model of type 2 diabetes mellitus.

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Namekawa, Junichi; Takagi, Yoshiichi; Wakabayashi, Kaoru; Nakamura, Yuki; Watanabe, Ayaka; Nagakubo, Dai; Shirai, Mitsuyuki; Asai, Fumitoshi

2017-06-10

Obesity and type 2 diabetes mellitus (T2DM) are occurring at epidemic-like rates, and these epidemics appear to have emerged largely from changes in daily diet. In the present study, we compared effects of high-fat diet (HFD) and fructose-rich diet (FRD) in WBN/Kob-Lepr fa (WBKDF) rats that spontaneously develop obesity, dyslipidemia and T2DM. After a 4-week feeding of each diet, WBKDF-HFD and WBKDF-FRD rats exhibited aggravated obesity and dyslipidemia compared with WBKDF rats fed standard diet (STD). In contrast, hyperglycemia developed in WBKDF-STD rats was significantly inhibited in WBKDF-FRD rats, but not in WBKDF-HFD rats. The present study demonstrated that the 4-week feeding of HFD and FRD caused diet-induced obesity with a distinct phenotype in the glucose metabolism in WBKDF rats.

High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

International Nuclear Information System (INIS)

Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Mehendale, Harihara M.

2008-01-01

Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD 10 dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-α, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 ± 14.0 nmol/min/g heart in ND versus 400.2 ± 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-α2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3

Effects of dihydropyridines on tension and calcium-45 influx in isolated mesenteric resistance vessels from spontaneously hypertensive and normotensive rats

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Cauvin, C.; Hwang, O.; Yamamoto, M.; van Breemen, C.

1987-01-01

Contractile tension responses to norepinephrine and depolarizing potassium (80 mM K+), as well as calcium-45 influx stimulated by these agents, were studied in isolated mesenteric resistance vessels (each 100 microM internal diameter) from spontaneously hypertensive rats (SHRs) and from normotensive Wistar Kyoto rats (WKYs). Inhibitory effects of 2 dihydropyridine Ca++ antagonists, PN 200-110 (isradipine) and nisoldipine, on these parameters were also determined. Contractile responses to 80 mM K+ were inhibited by both Ca++ antagonists with the same potency and efficacy in SHR compared with WKY vessels (PN 200-110 IC50 = 2.8 +/- 1.3 X 10(-8) M in SHRs and 2.5 +/- 1.5 X 10(-8) M in WKYs; nisoldipine IC50 = 1.1 +/- 0.4 X 10(-8) M in SHRs and 1.2 +/- 0.9 X 10(-8) M in WKYs). However, contractile responses to norepinephrine (10(-4) M) were inhibited less potently by nisoldipine in SHR vessels (IC50 = 2.2 +/- 0.3 X 10(-9) M) compared with WKY vessels (IC50 = 1.6 +/- 0.6 X 10(-10) M). Similarly, PN 200-110 tended to be less (but not significantly less) potent in SHR vessels (IC50 = 3.3 +/- 1.8 X 10(-8) M) than in WKY vessels (IC50 = 3.4 +/- 0.9 X 10(-9) M); its efficacy was significantly depressed in the SHR vessels (by approximately 20%). When norepinephrine-stimulated calcium-45 influx was determined in the presence of these Ca++ antagonists, a similar profile emerged with respect to a comparison of SHR and WKY vessels. These results support a previously hypothesized alteration in receptor-activated Ca++ influx pathways in SHR mesenteric resistance vessels

Metformin ameliorates diabetes but does not normalize the decreased GLUT 4 content in skeletal muscle of obese (fa/fa) Zucker rats

DEFF Research Database (Denmark)

Handberg, A; Kayser, L; Høyer, P E

1993-01-01

We studied the expression of the glucose transporter GLUT 4 in the soleus and red gastrocnemius muscles from obese, diabetic (fa/fa) Zucker rats compared to their lean littermates (Fa/-), with and without treatment with the antidiabetic drug metformin. In the untreated groups of rats, the GLUT 4...... content in a crude membrane fraction of both the soleus and the red gastrocnemius muscles were significantly lower in the obese (fa/fa) rats (3.46 +/- 0.28 vs. 6.04 +/- 0.41, p ... the same rats were confirmed by quantitative immunofluorescence microscopy, and the results were significantly correlated with the results obtained from quantitative immunoblotting (rho = 0.70, p fa/fa rats could contribute to the well-established insulin...

Early overfeed-induced obesity leads to brown adipose tissue hypoactivity in rats.

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de Almeida, Douglas L; Fabrício, Gabriel S; Trombini, Amanda B; Pavanello, Audrei; Tófolo, Laize P; da Silva Ribeiro, Tatiane A; de Freitas Mathias, Paulo C; Palma-Rigo, Kesia

2013-01-01

Brown adipose tissue activation has been considered a potential anti-obesity mechanism because it is able to expend energy through thermogenesis. In contrast, white adipose tissue stores energy, contributing to obesity. We investigated whether the early programming of obesity by overfeeding during lactation changes structure of interscapular brown adipose tissue in adulthood and its effects on thermogenesis. Birth of litters was considered day 0. On day 2, litter size was adjusted to normal (9 pups) and small (3 pups) litters. On day 21, the litters were weaned. A temperature transponder was implanted underneath interscapular brown adipose tissue pads of 81-day-old animals; local temperature was measured during light and dark periods between days 87 and 90. The animals were euthanized, and tissue and blood samples were collected for further analysis. The vagus and retroperitoneal sympathetic nerve activity was recorded. Small litter rats presented significant lower interscapular brown adipose tissue temperature during the light (NL 37.6°C vs. SL 37.2°C) and dark (NL 38°C vs. SL 37.6°C) periods compared to controls. Morphology of small litter brown adipose tissue showed fewer lipid droplets in the tissue center and more and larger in the periphery. The activity of vagus nerve was 19,9% greater in the small litter than in control (p<0.01), and no difference was observed in the sympathetic nerve activity. In adulthood, the small litter rats were 11,7% heavier than the controls and presented higher glycemia 13,1%, insulinemia 70% and corticosteronemia 92,6%. Early overfeeding programming of obesity changes the interscapular brown adipose tissue structure in adulthood, leading to local thermogenesis hypoactivity, which may contribute to obesity in adults. © 2013 S. Karger AG, Basel.

Similar metabolic responses to calorie restriction in lean and obese Zucker rats.

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Chiba, Takuya; Komatsu, Toshimitsu; Nakayama, Masahiko; Adachi, Toshiyuki; Tamashiro, Yukari; Hayashi, Hiroko; Yamaza, Haruyoshi; Higami, Yoshikazu; Shimokawa, Isao

2009-10-15

Calorie restriction (CR), which is thought to be largely dependent on the neuroendocrine system modulated by insulin/insulin-like growth factor-I (IGF-I) and leptin signaling, decreases morbidity and increases lifespan in many organisms. To elucidate whether insulin and leptin sensitivities are indispensable in the metabolic adaptation to CR, we investigated the effects of CR on obese Zucker (fa/fa) rats and lean control (+/+) rats. CR did not fully improve insulin resistance in (fa/fa) rats. Nonetheless, CR induced neuropeptide Y (NPY) expression in the hypothalamic arcuate nucleus and metabolism related gene expression changes in the liver in (fa/fa) rats and (+/+) rats. Up-regulation of NPY augmented plasma corticosterone levels and suppressed pituitary growth hormone (GH) expression, thereby modulating adipocytokine production to induce tissue-specific insulin sensitivity. Thus, central NPY activation via peripheral signaling might play a crucial role in the effects of CR, even in insulin resistant and leptin receptor deficient conditions.

Chronic vitamin A-enriched diet feeding regulates hypercholesterolaemia through transcriptional regulation of reverse cholesterol transport pathway genes in obese rat model of WNIN/GR-Ob strain

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Shanmugam M Jeyakumar

2016-01-01

Full Text Available Background & objectives: Hepatic scavenger receptor class B1 (SR-B1, a high-density lipoprotein (HDL receptor, is involved in the selective uptake of HDL-associated esterified cholesterol (EC, thereby regulates cholesterol homoeostasis and improves reverse cholesterol transport. Previously, we reported in euglycaemic obese rats (WNIN/Ob strain that feeding of vitamin A-enriched diet normalized hypercholesterolaemia, possibly through hepatic SR-B1-mediated pathway. This study was aimed to test whether it would be possible to normalize hypercholesterolaemia in glucose-intolerant obese rat model (WNIN/GR/Ob through similar mechanism by feeding identical vitamin A-enriched diet. Methods: In this study, 30 wk old male lean and obese rats of WNIN/GR-Ob strain were divided into two groups and received either stock diet or vitamin A-enriched diet (2.6 mg or 129 mg vitamin A/kg diet for 14 wk. Blood and other tissues were collected for various biochemical analyses. Results: Chronic vitamin A-enriched diet feeding decreased hypercholesterolaemia and normalized abnormally elevated plasma HDL-cholesterol (HDL-C levels in obese rats as compared to stock diet-fed obese groups. Further, decreased free cholesterol (FC and increased esterified cholesterol (EC contents of plasma cholesterol were observed, which were reflected in higher EC to FC ratio of vitamin A-enriched diet-fed obese rats. However, neither lecithin-cholesterol acyltransferase (LCAT activity of plasma nor its expression (both gene and protein in the liver were altered. On the contrary, hepatic cholesterol levels significantly increased in vitamin A-enriched diet fed obese rats. Hepatic SR-B1 expression (both mRNA and protein remained unaltered among groups. Vitamin A-enriched diet fed obese rats showed a significant increase in hepatic low-density lipoprotein receptor mRNA levels, while the expression of genes involved in HDL synthesis, namely, ATP-binding cassette protein 1 (ABCA1 and

Obesity reduces bone density associated with activation of PPARγ and suppression of Wnt/β-catenin in rapidly growing male rats.

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Jin-Ran Chen

Full Text Available BACKGROUND: It is well established that excessive consumption of a high fat diet (HFD results in obesity; however, the consequences of obesity on postnatal skeletal development have not been well studied. METHODOLOGY AND PRINCIPAL FINDINGS: Total enteral nutrition (TEN was used to feed postnatal day 27 male rats intragastrically with a high 45% fat diet (HFD for four weeks to induce obesity. Fat mass was increased compared to rats fed TEN diets containing 25% fat (medium fat diet, MFD or a chow diet (low fat diet, LFD fed ad libitum with matched body weight gains. Serum leptin and total non-esterified fatty acids (NEFA were elevated in HFD rats, which also had reduced bone mass compared to LFD-fed animals. This was accompanied by decreases in bone formation, but increases in the bone resorption. Bone marrow adiposity and expression of adipogenic genes, PPARγ and aP2 were increased, whereas osteoblastogenic markers osteocalcin and Runx2 were decreased, in bone in HFD rats compared to LFD controls. The diversion of stromal cell differentiation in response to HFD stemmed from down-regulation of the key canonical Wnt signaling molecule β-catenin protein and reciprocal up-regulation of nuclear PPARγ expression in bone. In a set of in vitro studies using pluripotent ST2 bone marrow mesenchymal stromal cells treated with serum from rats on the different diets or using the free fatty acid composition of NEFA quantified in rat serum from HFD-fed animals by GC-MS, we were able to recapitulate our in vivo findings. CONCLUSIONS/SIGNIFICANCE: These observations strongly suggest that increased NEFA in serum from rats made obese by HFD-feeding impaired bone formation due to stimulation of bone marrow adipogenesis. These effects of obesity on bone in early life may result in impaired attainment of peak bone mass and therefore increase the prevalence of osteoporosis later on in life.

Green tea polyphenols change the profile of inflammatory cytokine release from lymphocytes of obese and lean rats and protect against oxidative damage.

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Molina, N; Bolin, A P; Otton, R

2015-10-01

This study aimed to investigate whether green tea polyphenols (GT) modulate some functional parameters of lymphocytes from obese rats. Male Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight) and obesity was induced by cafeteria diet (8 weeks). Lymphocytes were obtained from mesenteric lymph nodes for analyses. In response to the cafeteria diet we observed an increase in activity of the metabolic enzyme hexokinase, ROS production, MnSOD, CuZnSOD and GR enzyme activities and proliferation capacity of the cells (baseline), whereas IL-10 production was decreased. Obese rats treated with GT decreased cell proliferation (under ConA stimulation). Hexokinase and G6PDH activity, ROS production and MnSOD, CuZnSOD, GPx and GR enzymes remained increased, accompanied by an increase in Nrf2 mRNA level. There was a decrease in pro-inflammatory IL-2, IL-6, IL-1β, TNF-α cytokines that were accompanied by a decrease in the mRNA level of TRL4 while IL-10 production was increased in obese rats treated with GT. GT treatment of lean rats showed similar results to that of obese rats treated with GT, indicating that the effects of GT are independent of diet. Foxp3 and IRF4 mRNA levels were increased by GT. In conclusion, cafeteria diet modulated the function of lymphocytes from lymph nodes, increasing ROS production and decreasing anti-inflammatory IL-10, which could contribute to the inflammatory state in obesity. GT reduced ROS production, improving the redox status and reducing pro-inflammatory cytokine production by lymphocytes, suggesting that GT treatment may be driving lymphocytes to a more anti-inflammatory than pro-inflammatory microenvironment. Copyright © 2015 Elsevier B.V. All rights reserved.

Resistant starch and exercise independently attenuate weight regain on a high fat diet in a rat model of obesity

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Johnson Ginger C

2011-07-01

Full Text Available Abstract Background Long-term weight reduction remains elusive for many obese individuals. Resistant starch (RS and exercise may be useful for weight maintenance. The effects of RS, with or without exercise, on weight regain was examined during relapse to obesity on a high carbohydrate, high fat (HC/HF diet. Methods Obesity-prone rats were fed ad libitum for 16 weeks then weight reduced on a low fat diet to induce a 17% body weight loss (weight reduced rats. Weight reduced rats were maintained on an energy-restricted low fat diet for 18 weeks, with or without a daily bout of treadmill exercise. Rats were then allowed free access to HC/HF diet containing low (0.3% or high (5.9% levels of RS. Weight regain, energy balance, body composition, adipocyte cellularity, and fuel utilization were monitored as rats relapsed to obesity and surpassed their original, obese weight. Results Both RS and exercise independently attenuated weight regain by reducing the energy gap between the drive to eat and suppressed energy requirements. Exercise attenuated the deposition of lean mass during relapse, whereas its combination with RS sustained lean mass accrual as body weight returned. Early in relapse, RS lowered insulin levels and reduced the deposition of fat in subcutaneous adipose tissue. Exercise cessation at five weeks of relapse led to increased weight gain, body fat, subcutaneous adipocytes, and decreased lean mass; all detrimental consequences to overall metabolic health. Conclusions These data are the first to show the complimentary effects of dietary RS and regular exercise in countering the metabolic drive to regain weight following weight loss and suggest that exercise cessation, in the context of relapse on a HC/HF diet, may have dire metabolic consequences.

Cardioprotective effect of L-glutamate in obese type 2 diabetic Zucker fatty rats

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Povlsen, Jonas Agerlund; Løfgren, Bo; Rasmussen, Lars Ege

2009-01-01

(Wistar-Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area-at-risk (AAR) ratio was the primary end-point. Expression of L-glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative...... was downregulated in hearts from ZDF rats at both the mRNA and protein levels (P diabetic hearts (P obese diabetic rats have......1. Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by L-glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that L-glutamate-mediated postischaemic cardioprotection...

Anti-obesity effects of tea from Mangifera indica L. leaves of the Ubá variety in high-fat diet-induced obese rats.

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Ramírez, Natalia Medina; Toledo, Renata C Lopes; Moreira, Maria E Castro; Martino, Hércia Stampini Duarte; Benjamin, Laércio Dos Anjos; de Queiroz, José H; Ribeiro, Andréia Queiroz; Ribeiro, Sônia Machado Rocha

2017-07-01

Due to the high content of bioactive compounds, herbal teas are being investigated as adjuvant in chronic disease management. Studies have shown that mango leaf tea contain mangiferin, total phenolics and antioxidants, compounds with many functional properties. Therefore, this study aims to evaluate the anti-obesity effects of tea from Mangifera indica L. leaves, Ubá variety (TML), in obese rats fed a high-fat diet (HFD). For this, adult male Wistar rats were divided into three groups (n=8): the control group (fed AIN-93 diet), obese group (fed a HFD) and treated group (fed a HFD and supplemented with TML for 8 weeks). We analysed biometric measures and serum biochemical parameters of metabolic control, inflammation and oxidative stress biomarkers, histomorphometry of visceral adipose tissue and mRNA expression of peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PPAR-γ), lipoprotein lipase (LPL) and fatty acid synthase (FAS). The consumption of TML (24.7±2.1mL/day) exerted antioxidant and anti-inflammatory effects, increasing total antioxidant capacity and interleukin-10 serum concentrations, reduced abdominal fat accumulation, upregulated PPAR-γ and LPL and downregulated FAS expression. Our data suggest that TML has therapeutic potential in treating obesity and related diseases through regulating the expression of transcriptional factors and enzymes associated with adipogenesis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effects of yam dioscorin interventions on improvements of the metabolic syndrome in high-fat diet-induced obese rats.

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Shih, Shen-Liang; Lin, Yin-Shiou; Lin, Shyr-Yi; Hou, Wen-Chi

2015-12-01

The metabolic syndrome (MS) is termed a cluster of multiple metabolic risk criteria which is positively correlated with cardiovascular disease and type 2 diabetes mellitus (DM). Yam dioscorins have been reported to exhibit biological activities, however, little is known their preventive effects on the MS. Therefore, a high-fat (HF) diet was used to induce Wistar rat obesity and then yam dioscorin (50 mg/kg, dio50) was intervened daily concurrent HF diet (HF diet + dio50) for five weeks to check the changes of weights of body and tissues, blood pressures, and impaired glucose tolerances. The in vitro peptic hydrolysates of dioscorin with molecular mass between 3 kDa and 10 kDa and less than 3 kDa were used to determine dipeptidyl peptidase IV (DPP IV) inhibitory activities which DPP IV inhibitor has been reported to prevent and treat type 2 DM. There were no significant difference in body weights, feed intakes, feed conversion, and weights of adipose tissues of obese rats in groups of HF and (HF diet + dio50). However, the systolic blood pressures in obese rats of 2-, 3- and 4-week dioscorin interventions were showed significantly lower (P dioscorin intervention (HF+ dio50) was showed significantly different (P dioscorin peptic hydrolysates (5 mg/ml) showed inhibitory activities against DPP IV using sitagliptin phosphate as positive controls. Yam dioscorins exhibit improved MS activities in obese rats which the related mechanisms may need further investigations.

Perfil nutricional e cardiovascular de ratos normotensos e hipertensos sob dieta hiperlipídica Perfil nutricional y cardiovascular de ratas normotensas e hipertensos bajo dieta hiperlipídica Nutritional and cardiovascular profiles of normotensive and hypertensive rats kept on a high fat diet

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Silvio A. Oliveira Júnior

2009-11-01

contempló la presión arterial sistólica (PAS, evaluación cardiopulmonar anatómica, ecocardiograma e histología cardiaca. RESULTADOS: Las SHRs presentaron menor PC, adiposidad, glucosa, colesterol, triacilglicerol, leptina e insulina, cuando comparadas a las WKYs. En las SHR, la ingestión calórica aumentó con la DH. Sin embargo en las WKYs, la DH elevó la eficiencia energética, la adiposidad y la leptina y reduzco la glucemia. En la evaluación cardiovascular, las SHR presentaron mayor PAS, humedad pulmonar, hipertrofia y fibrosis intersticial miocárdica en cuanto a las WKYs (pBACKGROUND: Although a high fat diet (HFD promotes nutritional and heart disorders, few studies have assessed its influence in normotensive Wistar-Kyoto rats (WKY and spontaneously hypertensive rats (SHR. OBJECTIVE: To evaluate and compare the nutritional and cardiovascular profiles of WKY and SHR on a high fat diet. METHODS: 20 WKY and 20 SHR were divided into four groups: Control-WKY (C-WKY, HFD-WKY, Control-SHR (C-SHR and HFD-SHR. The C and HFD groups received, respectively, a normocaloric diet and a HFD for 20 weeks. The following features were evaluated: body weight (BW, adiposity, blood glucose, serum lipids, with measurements of total cholesterol and triacylglycerol levels, insulin and leptin. The cardiovascular study included the systolic blood pressure (SBP, a cardiopulmonary anatomical evaluation, an echocardiography and heart histology. RESULTS: The SHR had BW, adiposity, glucose, cholesterol, triacylglycerol, leptin and insulin levels lower than the WKY. In SHR, the caloric intake increased with HFD. In WKY, the HFD increased energy efficiency, adiposity and blood leptin, and reduced glucose. In the cardiovascular assessment, the SHR had SBP, pulmonary moisture, myocardial hypertrophy and interstitial fibrosis higher than the WKY (p <0.01; the cardiac function was similar in both strains. The HFD reduced the ventricular systolic diameter in the WKY and increased the mitral E

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

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R.M. Banin

2014-09-01

Full Text Available Ginkgo biloba extract (GbE has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1, protein tyrosine phosphatase 1B (PTP-1B, and protein kinase B (Akt, as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD or a normal fat diet (NFD for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V, and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb. NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

International Nuclear Information System (INIS)

Banin, R.M.; Hirata, B.K.S.; Andrade, I.S.; Zemdegs, J.C.S.; Clemente, A.P.G.; Dornellas, A.P.S.; Boldarine, V.T.; Estadella, D.; Albuquerque, K.T.; Oyama, L.M.; Ribeiro, E.B.; Telles, M.M.

2014-01-01

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Energy Technology Data Exchange (ETDEWEB)

Banin, R. M.; Hirata, B. K.S. [Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP (Brazil); Andrade, I. S.; Zemdegs, J. C.S. [Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Clemente, A. P.G. [Faculdade de Nutrição, Universidade Federal de Alagoas, Maceió, AL (Brazil); Dornellas, A. P.S.; Boldarine, V. T. [Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Estadella, D. [Departamento de Biociências, Universidade Federal de São Paulo, Baixada Santista, SP (Brazil); Albuquerque, K. T. [Curso de Nutrição, Universidade Federal do Rio de Janeiro, Macaé, RJ (Brazil); Oyama, L. M.; Ribeiro, E. B. [Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Telles, M. M. [Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP (Brazil)

2014-07-25

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats

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Shitalkumar P Zambad

2011-01-01

Full Text Available Shitalkumar P Zambad1, Siralee Munshi2, Amita Dubey3, Ram Gupta1, Rosa Anna Busiello4, Antonia Lanni5, Fernando Goglia6, Ramesh C Gupta7, Vijay Chauthaiwale8, Chaitanya Dutt91Pharmacology, 2Cellular and Molecular Biology, 3Pre-clinical and Safety Evaluation, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gujarat, India; 4Dipartimento di Biologia, Universita degli Studi di Napoli Federico II, Naples, Italy; 5Dipartimento di Scienze della Vita, Seconda Universita di Napoli, Caserta, Italy; 6Dipartimento di Scienze Biologiche ed Ambientali, Universita del Sannio, Benevento, Italy; 7Medicinal Chemistry, 8Discovery Research, 9Clinical Research, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gujarat, IndiaAbstract: Chronic overnutrition and consequential visceral obesity is associated with a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. Moreover, individuals who have a triad of hypertension, dysglycemia, and elevated triglycerides along with reduced high-density lipoprotein cholesterol have a greater residual cardiovascular risk even after factoring for the traditional risk factors such as age, smoking, diabetes, and elevated low-density lipoprotein cholesterol. In our previous study we demonstrated that TRC150094, when administered to rats receiving a high-fat diet, stimulated mitochondrial fatty acid oxidation (FAO and reduced visceral adiposity, opening an interesting perspective for a possible clinical application. In the present study, oral administration of TRC150094 to obese Zucker spontaneously hypertensive fatty rats (obese ZSF1 improved glucose tolerance and glycemic profile as well as attenuated a rise in blood pressure. Obese ZSF1 rats treated with TRC150094 also showed reduced hepatic steatosis, reduced progression of nephropathy, and improved skeletal muscle function. At the cellular level, TRC150094 induced a significant increase in mitochondrial respiration as well as an increased FAO in

Biochemical Study of Oxidative Stress Markers in the Liver, Kidney and Heart of High Fat Diet Induced Obesity in Rats

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Noeman Saad A

2011-08-01

Full Text Available Abstract Background Obesity has become a leading global health problem owing to its strong association with a high incidence of diseases. Aim To induce rat obesity using high fat diet (HFD and to estimate oxidative stress markers in their liver, heart and kidney tissues in order to shed the light on the effect of obesity on these organs. Materials and methods Sixty white albino rats weighing 150-200 g were randomly divided into two equal groups; group I: received high fat diet for 16 weeks, and group II (control group: received only normal diet (rat chow for 16 weeks. Blood samples were taken for measurement of lipid profile, tissue samples from liver, heart and kidney were taken for determination of malondialdehyde (MDA, protein carbonyl (PCO, reduced glutathione (GSH levels, and the activities of glutathione S- transferase (GST glutathione peroxidase (GPx, catalase (CAT and paraoxonase1 (PON1 enzymes. Results Data showed that feeding HFD diet significantly increased final body weight and induced a state of dyslipideamia. Also our results showed a significant increase MDA and PCO levels in the hepatic, heart and renal tissues of obese rats, as well as a significant decrease in the activity of GST, GPx and PON 1 enzymes. On the other hand CAT enzyme activity showed significant decrease only in renal tissues of obese rats with non significant difference in hepatic and heart tissues. GSH levels showed significant decrease in both renal and hepatic tissues of obese animals and significant increase in their heart tissues. Correlation studies in obese animals showed a negative correlation between MDA and PCO tissue levels and the activities of GPx, GST and PON1 in all tissues and also with CAT enzyme activity in renal tissues. Also a negative correlation was detected between MDA & PCO tissues levels and GSH levels in both hepatic and renal tissues. While positive correlation was found between them and GSH levels in heart tissues. Conclusion High fat

A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance

OpenAIRE

Bosse, John D.; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E. Dale; Pereira, Troy J.; Dolinsky, Vernon W.; Symons, J. David; Jalili, Thunder

2013-01-01

Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-...