scholarly journals Chronic administration of AM251 improves albuminuria and renal tubular structure in obese rats

2015 ◽  
Vol 225 (2) ◽  
pp. 113-124 ◽  
Author(s):  
Kayte A Jenkin ◽  
Lannie O'Keefe ◽  
Anna C Simcocks ◽  
Esther Grinfeld ◽  
Michael L Mathai ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Chronic Administration ◽  
Sprague Dawley ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Obese Rats ◽  
Renal Tubular ◽  
Plasma Leptin

Modulation of the endocannabinoid system as an anti-obesity therapeutic is well established; however, the direct effects of cannabinoid receptor 1 (CB1) antagonism on renal function and structure in a model of diet-induced obesity (DIO) are unknown. The aim of this study was to characterise the renal effects of the CB1 antagonist AM251 in a model of DIO. Male Sprague–Dawley rats were fed a low- or high-fat diet (HFD: 40% digestible energy from lipids) for 10 weeks to elicit DIO (n=9). In a different cohort, rats were fed a HFD for 15 weeks. After 9 weeks consuming a HFD, rats were injected daily for 6 weeks with 3 mg/kg AM251 (n=9) or saline via i.p. injection (n=9). After 10 weeks consuming a HFD, CB1 and megalin protein expression were significantly increased in the kidneys of obese rats. Antagonism of CB1 with AM251 significantly reduced weight gain, systolic blood pressure, plasma leptin, and reduced albuminuria and plasma creatinine levels in obese rats. Importantly, there was a significant reduction in tubular cross-section diameter in the obese rats treated with AM251. An improvement in albuminuria was likely due to the reduction in tubular size, reduced leptinaemia and maintenance of megalin expression levels. In obese rats, AM251 did not alter diastolic blood pressure, sodium excretion, creatinine clearance or expression of the fibrotic proteins VEGFA, TGFB1 and collagen IV in the kidney. This study demonstrates that treatment with CB1 antagonist AM251 improves renal outcomes in obese rats.

Defense of differfing body weight set points in diet-induced obese and resistant rats

1998 ◽  
Vol 274 (2) ◽  
pp. R412-R419 ◽  
Author(s):  
Barry E. Levin ◽  
Richard E. Keesey
Keyword(s):  
Body Weight ◽  
Diet Composition ◽  
Energy Homeostasis ◽  
Energy Content ◽  
Sprague Dawley ◽  
Fat Pad ◽  
Insulin Levels ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Plasma Leptin

Among outbred Sprague-Dawley rats, approximately one-half develop diet-induced obesity (DIO) and one-half are diet resistant (DR) on a diet relatively high in fat and energy content (HE diet). Here we examined the defense of body weight in these two phenotypes. After HE diet for 13 wk, followed by chow for 6 wk, DR rats gained weight comparably but their plasma leptin levels fell to 54% of chow-fed controls. When a palatable liquid diet (Ensure) was added for 13 wk, other DR rats became obese. But when switched to chow, their intakes fell by 60%, and body and retroperitoneal (RP) fat pad weights and plasma leptin and insulin levels all declined for 2 wk and then stabilized at control levels after 6 wk. In contrast, comparably obese DIO rats decreased their intake by only 20%, and their weights plateaued when they were switched to chow after 13 wk on HE diet. When a subgroup of these DIO rats was restricted to 60% of prior intake, their weights fell to chow-fed control levels over 2 wk. But their leptin and insulin levels both fell disproportionately to 30% of controls. When no longer restricted, their intake and feed efficiency rose immediately, and their body and RP pad weights and leptin and insulin levels rose to those of unrestricted DIO rats within 2 wk. Thus diet and genetic background interact to establish high (DIO) or low (DR) body weight set points, which are then defended against subsequent changes in diet composition and/or energy availability. If leptin affects energy homeostasis, it does so differentially in DIO vs. DR rats since comparably low and high levels were associated with differing patterns of weight change between the two phenotypes.

Ontogeny of diet-induced obesity in selectively bred Sprague-Dawley rats

2003 ◽  
Vol 285 (3) ◽  
pp. R610-R618 ◽  
Author(s):  
Matthew R. Ricci ◽  
Barry E. Levin
Keyword(s):  
Leptin Receptor ◽  
Splice Variants ◽  
Caloric Intake ◽  
High Energy ◽  
Sprague Dawley ◽  
Low Fat Diet ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Sprague Dawley Rats ◽  
Plasma Leptin

Outbred Sprague-Dawley rats selectively bred for their propensity to develop diet-induced obesity (DIO) become heavier on low-fat diet than those bred to be diet resistant (DR) beginning at ∼5 wk of age. Here we assessed the development of metabolic and neural functions for insights into the origins of their greater weight gain. From week 5 to week 10, chow-fed DIO rats gained 15% more body weight and ate ∼14% more calories but had only slightly greater adiposity and plasma leptin than DR rats. From day 3 through week 10, DIO and DR rats had similar mRNA expression of arcuate nucleus neuropeptide Y, proopiomelanocortin, agouti-related peptide, and all splice variants of the leptin receptor (OB-R). When fed a high-energy (HE; 31% fat) diet, 7-wk-old DIO rats had a 240% increase in plasma leptin levels after only 3 days. Despite this early leptin rise, they maintained a persistent hyperphagia and became more obese than chow-fed DIO rats and DR rats fed chow or HE diet. Their failure to reduce caloric intake, despite high levels of leptin, suggests that selectively bred DIO rats might have reduced leptin sensitivity similar to that seen in the outbred DIO parent strain.

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

2009 ◽  
Vol 87 (11) ◽  
pp. 900-907 ◽  
Author(s):  
H.P. Chudasama ◽  
P.A. Bhatt
Keyword(s):  
Blood Pressure ◽  
Food Intake ◽  
Body Mass ◽  
Tail Suspension Test ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Noradrenaline Reuptake ◽  
Obese Rats ◽  
Secondary Objective ◽  
Swimming Test

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·kg–1, p.o.) and sibutramine (5 mg·kg–1, p.o.) for 4 weeks. Control animals were treated with duloxetine alone (30 mg·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.

Obesity-Induced Hypertension Develops in Young Rats Independently of the Renin-Angiotensin-Aldosterone System

2006 ◽  
Vol 231 (3) ◽  
pp. 282-287 ◽  
Author(s):  
Anita D. Smith ◽  
Michael W. Brands ◽  
Mong-Heng Wang ◽  
Anne M. Dorrance
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Vascular Reactivity ◽  
Fasting Blood Glucose ◽  
Plasma Renin ◽  
Diet Group ◽  
Sprague Dawley ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Induced Hypertension

A correlation exists between obesity and hypertension. In the currently available models of diet-induced obesity, the treatment of rats with a high fat (HF) diet does not begin until adulthood. Our aim was to develop and characterize a model of pre-pubescent obesity-induced hypertension. Male Sprague-Dawley rats were fed a HF diet (35% fat) for 10 weeks, beginning at age 3 weeks. Blood pressure was measured by tail-cuff, and a terminal blood sample was obtained to measure fasting blood glucose, insulin, plasma renin, aldosterone, thiobarbitutic acid reactive substances (TBARS), and free 8-isoprostanes levels. The vascular reactivity in the aorta was assessed using a myograph. Blood pressure was increased in rats fed the HF diet (HF, 161 ± 2 mm Hg vs. control, 137 ± 2 mm Hg, P < 0.05). Blood glucose (HF, 155 ± 4 mg/dL vs. control, 123 ± 5 mg/dL, P < 0.05), insulin (HF, 232 ± 63 pM vs. control, 60 ± 11 pM, P < 0.05), TBARS (expressed as nM of malondialdehyde [MDA]/ml [HF, 1.8 ± 0.37 nM MDA/ml vs. control 1.05 ± 0.09 nM MDA/ml, P < 0.05]), and free 8-isoprostanes (HF, 229 ± 68 pg/ml vs. control, 112 ± 9 pg/ml, P < 0.05) levels were elevated in the HF diet group. Interestingly, plasma renin and aldosterone levels were not different between the groups. The maximum vasoconstriction to phenylephrine (10−4 M) was increased in the HF diet group (HF, 26.1 ± 1.5 mN vs. control 22.3 ± 1.2 mN, P < 0.05). In conclusion, pre-pubescent rats become hypertensive and have increased oxidative stress and enhanced vasoconstriction when fed a HF diet. Surprisingly, this occurs without the increase in renin or aldosterone levels seen in the adult models of diet-induced obesity.

scholarly journals Standard housing temperature but not β3-adrenoreceptor agonism drives weight-gain and adipose tissue deposition in rats following diet induced obesity at thermoneutrality

2019 ◽  
Author(s):  
Peter Aldiss ◽  
Jo E Lewis ◽  
Irene Lupini ◽  
David Boocock ◽  
Amanda K Miles ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Subcutaneous Fat ◽  
Chronic Administration ◽  
Histone Deacetylation ◽  
Sprague Dawley ◽  
Diet Induced Obesity ◽  
Housing Temperature ◽  
Skeletal Muscle Contraction ◽  
Sprague Dawley Rats

AbstractBackground and aimRodents are commonly housed below thermoneutrality and this exposure to ‘cold’ (i.e. 20°C) activates thermogenic brown (BAT) and beiging of white adipose tissue. Here, we examined whether a standard housing temperature (i.e. 20°C, a reduction in temperature of ∼8°C) or YM-178, a highly-selective β3-adrenoreceptor agonist, in obese animals raised at thermoneutrality, would impact differently on classical BAT or subcutaneous inguinal (IWAT) beige depots.MethodsEighteen weanling Sprague-Dawley rats were housed at thermoneutrality (28°C) and fed a high-fat diet. At 12 weeks, 6 animals were randomised to either standard housing temperature (20°C, n=6) or to β3-A R agonist administration (28°C+ β3, 0.75mg/kg/d, n=6) for 4 weeks. Metabolic assessment was undertaken during the final 48h, followed by interscapular, perivascular BAT and IWAT sampling for the analysis of thermogenic genes and the proteome.ResultsExposure to 20°C increased weight gain, BAT and IWAT mass. Proteomic analysis of BAT revealed novel pathways associated with cold-induced weight gain (i.e. histone deacetylation, glycosaminoglycan degradation and glycosphingolipid biosynthesis) whilst β3- adrenoreceptor agonism impacted on proteins involved in skeletal muscle contraction and cell differentiation. IWAT of cold-exposed animals exhibited an enrichment of proteins involved NAD+ binding, plus retinol and tyrosine metabolic pathways whilst β3-AR agonism downregulated ribosomal and upregulated acute phase response proteins.ConclusionFollowing diet-induced obesity at thermoneutrality, exposure to 20°C promotes subcutaneous fat deposition in order to reduce heat loss and defend body temperature. In contrast, chronic administration of β3-AR agonist has minimal metabolic-related effects on adipose tissue.

scholarly journals Dietary obesity increases NO and inhibits BKCa-mediated, endothelium-dependent dilation in rat cremaster muscle artery: association with caveolins and caveolae

2012 ◽  
Vol 302 (12) ◽  
pp. H2464-H2476 ◽  
Author(s):  
Lauren Howitt ◽  
T. Hilton Grayson ◽  
Margaret J. Morris ◽  
Shaun L. Sandow ◽  
Timothy V. Murphy
Keyword(s):  
Control Diet ◽  
Cremaster Muscle ◽  
Sprague Dawley ◽  
High Fat ◽  
Caveolin 1 ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Dependent Component ◽  
Obese Rats ◽  
Dietary Obesity

Obesity is a risk factor for hypertension and other vascular disease. The aim of this study was to examine the effect of diet-induced obesity on endothelium-dependent dilation of rat cremaster muscle arterioles. Male Sprague-Dawley rats (213 ± 1 g) were fed a cafeteria-style high-fat or control diet for 16–20 wk. Control rats weighed 558 ± 7 g compared with obese rats 762 ± 12 g ( n = 52–56; P < 0.05). Diet-induced obesity had no effect on acetylcholine (ACh)-induced dilation of isolated, pressurized (70 mmHg) arterioles, but sodium nitroprusside (SNP)-induced vasodilation was enhanced. ACh-induced dilation of arterioles from control rats was abolished by a combination of the KCa blockers apamin, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), and iberiotoxin (IBTX; all 0.1 μmol/l), with no apparent role for nitric oxide (NO). In arterioles from obese rats, however, IBTX had no effect on responses to ACh while the NO synthase (NOS)/guanylate cyclase inhibitors Nω-nitro-l-arginine methyl ester (l-NAME; 100 μmol/l)/1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μmol/l) partially inhibited ACh-induced dilation. Furthermore, NOS activity (but not endothelial NOS expression) was increased in arteries from obese rats. l-NAME/ODQ alone or removal of the endothelium constricted arterioles from obese but not control rats. Expression of caveolin-1 and -2 oligomers (but not monomers or caveolin-3) was increased in arterioles from obese rats. The number of caveolae was reduced in the endothelium of arteries, and caveolae density was increased at the ends of smooth muscle cells from obese rats. Diet-induced obesity abolished the contribution of large-conductance Ca2+-activated K+ channel to ACh-mediated endothelium-dependent dilation of rat cremaster muscle arterioles, while increasing NOS activity and inducing an NO-dependent component.

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

2005 ◽  
Vol 289 (2) ◽  
pp. R373-R379 ◽  
Author(s):  
Kimberly A. Singh ◽  
Carol N. Boozer ◽  
Joseph R. Vasselli
Keyword(s):  
Sprague Dawley ◽  
Short Term ◽  
Feeding Inhibition ◽  
Fasted State ◽  
Sprague Dawley Rats ◽  
Or Groups ◽  
Body Weights ◽  
Obese Rats ◽  
Rat Adipose Tissue ◽  
Plasma Leptin

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.

scholarly journals Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension

2008 ◽  
Vol 295 (5) ◽  
pp. R1546-R1554 ◽  
Author(s):  
Melissa Li ◽  
Xiaoling Dai ◽  
Stephanie Watts ◽  
David Kreulen ◽  
Gregory Fink
Keyword(s):  
Blood Pressure ◽  
Sympathetic Innervation ◽  
Sympathetic Ganglia ◽  
Plasma Norepinephrine ◽  
Sprague Dawley ◽  
Surgical Ablation ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Hypertension Development

Endothelin (ET) type B receptors (ETBR) are expressed in multiple tissues and perform different functions depending on their location. ETBR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ETBR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia.

Sign in / Sign up

Export Citation Format

Share Document