Abstract 198: Oral Administration of the Mas Agonist A-1317 Produces Beneficial Cardiometabolic Effects in Rats

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Suellen F Vilas Boas ◽  
Janaina F Braga ◽  
Analina R Silva ◽  
Mariana F Oliveira ◽  
Robson A S Santos
Keyword(s):  
Body Weight ◽  
Glucose Tolerance ◽  
Inclusion Compound ◽  
Metabolic Diseases ◽  
Spontaneously Hypertensive Rat ◽  
Body Weight Gain ◽  
The Body ◽  
Oral Glucose ◽  
Sprague Dawley ◽  
Tissue Mass

The beneficial effects of the Mas/Ang-(1-7) pathway prompted us to develop novel Ang-(1-7) analogues and ligands for Mas. In the present study, we evaluated the cardiometabolic effects of a pharmacological formulation developed by including the Mas agonist A-1317 in hydroxypropyl β-cyclodextrin (HPβCD). The inclusion compound was given orally (10 μg/Kg body weight) to Spontaneously hypertensive rat (SHR) and fructose-fed rats. Mean arterial pressure (MAP) and heart rate (HR) were monitored for 5 hours after administration of a single dose of A-1317-HPβCD in conscious SHR. Seven-weeks-old male Sprague-Dawley rats were fed with either normal rat chow (CTL) or the same diet plus 10% fructose in the drinking water (FFR). For the last 4 wk of a 9-wk period of each diet, a subgroup of each group of animals was treated daily with the oral A-1317 (CTL-A or FFR-A) or with vehicle (CTL-V or FFR-V). Rats were subjected to oral glucose tolerance test (2 g/Kg body weight) concomitantly with the evaluation of plasma insulin levels. A-1317 reduced MAP with the maximum change occurring after 4 hours of administration (Δ=-23±2mmHg). There was no significant effect of A-1317 on HR of SHR. Once a day administration of A-1317 ameliorated all metabolic conditions altered by fructose-feed, including the glucose tolerance with less release of insulin and the decreased in the basal insulinemia. However no change in glycemia was observed. Regarding the lipidic metabolism, there was a decrease in the hepatic and serum tryacilglicerol levels (CTL-V=51±3; CTL-A=44±4; FFR-V=74±6; FFR-A=45±5 mg/dl serum levels), the body weight gain and the epididymal and mesenteric adipose tissue mass. Moreover hepatic and serum cholesterol levels were surprisingly diminished in both treated groups. These data suggest that A-1317 inclusion compound is an innovative therapeutic tool for treatment the cardiovascular and metabolic diseases.

No effect of dietary calcium on body weight of lean and obese mice and rats

2004 ◽  
Vol 286 (4) ◽  
pp. R669-R677 ◽  
Author(s):  
Qinmin Zhang ◽  
Michael G. Tordoff
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Calcium Content ◽  
High Energy ◽  
Dietary Calcium ◽  
Simple Relation ◽  
Normal Weight ◽  
The Body ◽  
High Energy Density ◽  
Sprague Dawley

Recent epidemiological and animal studies have led to the hypothesis that low dietary calcium intakes contribute to obesity. Here, we evaluated whether calcium influenced the body weight of normal-weight and obese rodents. All experiments involved female C57BL/6J mice or Sprague-Dawley rats fed normal- or high-energy-density diets (3.8 or 4.7 kcal/g). Calcium intake was manipulated by allowing mice to drink sweetened 30 mM CaCl2 solution or feeding mice and rats diets differing in calcium content (0.2%, 0.6%, or 1.8% Ca2+). Blood samples were taken from rats to confirm that the diets had their intended effects on metabolism. There were no effects of the calcium manipulations on energy intake, body weight, or carcass fat content and no simple relation between calciotropic hormones and body weight. One experiment found a significant decrease in body weight gain of lean and obese rats fed the 1.8% Ca2+ diet, but we suspect that this was due to forced consumption of the unpalatable diet, reducing growth. These studies provide little support for the hypothesis that dietary calcium contributes to the etiology or maintenance of obesity.

scholarly journals Stress facilitates body weight gain in genetically predisposed rats on medium-fat diet

2003 ◽  
Vol 285 (4) ◽  
pp. R791-R799 ◽  
Author(s):  
Chantal Michel ◽  
Barry E. Levin ◽  
Ambrose A. Dunn-Meynell
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Dentate Gyrus ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
High Energy ◽  
The Body ◽  
Central Nucleus ◽  
Sprague Dawley ◽  
Dorsomedial Nucleus

To assess the interaction between stress and energy homeostasis, we immobilized male Sprague-Dawley rats prone to diet-induced obesity (DIO) or diet resistance (DR) once for 20 min and then fed them either low-fat (4.5%) chow or a medium-fat (31%), high-energy (HE) diet for 9 days. Stressed, chow-fed DIO rats gained less, while stressed DIO rats on HE diet gained more body weight and had higher feed efficiency and plasma leptin levels than unstressed controls. Neither stress nor diet affected DR body weight gain. While stress-induced plasma corticosterone levels did not differ between phenotypes, DIO rats were initially more active in an open field and had higher hippocampal dentate gyrus and CA1 glucocorticoid receptor (GR) mRNA than DR rats, regardless of prior stress or diet. HE diet intake was associated with raised dentate gyrus and CA1 GR and amygdalar central nucleus (CeA) corticotropin-releasing hormone (CRH) mRNA expression, while stress was associated with reduced hypothalamic dorsomedial nucleus Ob-R mRNA and CeA CRH specifically in DIO rats fed HE diet. Thus a single stress triggers a complex interaction among weight gain phenotype, diet, and stress responsivity, which determines the body weight and adiposity of a given individual.

scholarly journals Effects of multiple cycles of weight loss and regain on the body weight regulatory system in rats

2019 ◽  
Vol 317 (5) ◽  
pp. E863-E870 ◽  
Author(s):  
Jennifer L. Rosenbaum ◽  
R. Scott Frayo ◽  
Susan J. Melhorn ◽  
David E. Cummings ◽  
Ellen A. Schur
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Glucose Tolerance ◽  
Regulatory System ◽  
The Body ◽  
Oral Glucose ◽  
Positive Effects ◽  
Multiple Cycles ◽  
Ad Libitum ◽  
Ad Libitum Feeding

We studied the effects of multiple cycles of weight loss and regain on the defended body weight in rats. Thirty-six male Wistar rats were divided into three weight-matched groups: weight cyclers ( n = 18), ad libitum-fed controls ( n = 9), and maturity controls ( n = 9). Cyclers underwent four rounds of 20% weight loss from 50% caloric restriction, each cycle followed by recovery to stable plateau weight on ad libitum feeding. Controls ate ad libitum. Maturity controls ate ad libitum and then weight cycled the final two rounds to evaluate the effect of age in later cycles. Cyclers’ postdiet plateau weight became progressively lower than that of controls. With each weight loss, ghrelin increased, while insulin and leptin decreased; the magnitude of these changes did not differ across cycles. After four rounds, cyclers’ weight (504 ± 7 vs. 540 ± 22 g; P < 0.05) and percent body fat (11.7 vs. 15.2%; P < 0.05) were lower than in controls. After a 4-mo follow-up period of ad libitum feeding, cyclers maintained a lower total fat-pad mass versus controls (8.6 ± 0.5 vs. 15.9 ± 3.6 g; P < 0.01) and a lower glucose area-under-the-curve on oral glucose tolerance tests ( P < 0.05). Repeated weight-loss cycles exerted positive effects, durably lowering defended levels of body adiposity and improving glucose tolerance.

scholarly journals Carbohydrate-Responsive Gene Expression in the Adipose Tissue of Rats

Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 153-164 ◽  
Author(s):  
Kartik Shankar ◽  
Amanda Harrell ◽  
Ping Kang ◽  
Rohit Singhal ◽  
Martin J. J. Ronis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Composition ◽  
Body Weight ◽  
Adipose Tissue ◽  
Body Weight Gain ◽  
Caloric Intake ◽  
Oral Glucose ◽  
Sprague Dawley ◽  
Simple Carbohydrates ◽  
The Impact

Abstract Although obesity is often associated with high-fat diets, it can develop from a variety of meal patterns. Excessive intake of simple carbohydrates is one consistent eating behavior leading to obesity. However, the impact of overconsumption of diets with high carbohydrate to fat ratios (C/F) on body composition and global adipose tissue gene expression remains unclear. We used total enteral nutrition to evaluate the effects of caloric intake and C/F on body weight gain and development of obesity. Female Sprague Dawley rats were fed diets with either low C/F or high C/F (HC) (reflecting a 19.5-fold increase in C/F) at two levels of caloric intake: 187 or 220 kcal/kg3/4 · d (15% excess) for 4 wk. At the end of the study period, rats fed HC diets had about 20% higher body weight at either caloric intake compared with rats fed low C/F diets (P &lt; 0.05). Body composition (assessed by nuclear magnetic resonance, computerized tomography, and adipose tissue weights) revealed higher percent fat mass (P &lt; 0.05) in HC rats. Obesity was associated with increased serum resistin, leptin, fasting hyperinsulinemia, and insulin resistance after an oral glucose challenge (P &lt; 0.05). Microarray analyses of adipose tissues revealed HC diets led to changes in 270 and 464 transcripts at 187 and 220 kcal/kg3/4 · d intakes. Genes regulating glucose transport, glycolysis, fatty acid and triglyceride biosynthesis, desaturation and elongation, adipogenesis, and adipokines were affected by HC diets. These results suggest that C/F and interactions with excessive caloric intake per se may regulate body composition and play important roles in the development of obesity and metabolic syndrome.

scholarly journals The Effect of Isoleucine Supplementation on Body Weight Gain and Blood Glucose Response in Lean and Obese Mice

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2446
Author(s):  
Rebecca O’Rielly ◽  
Hui Li ◽  
See Meng Lim ◽  
Roger Yazbeck ◽  
Stamatiki Kritas ◽  
...  
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Weight Gain ◽  
Gastric Emptying ◽  
Glucose Tolerance ◽  
Body Weight Gain ◽  
Oral Glucose ◽  
Obese Mice ◽  
Glucose Response ◽  
The Impact

Chronic isoleucine supplementation prevents diet-induced weight gain in rodents. Acute-isoleucine administration improves glucose tolerance in rodents and reduces postprandial glucose levels in humans. However, the effect of chronic-isoleucine supplementation on body weight and glucose tolerance in obesity is unknown. This study aimed to investigate the impact of chronic isoleucine on body weight gain and glucose tolerance in lean and high-fat-diet (HFD) induced-obese mice. Male C57BL/6-mice, fed a standard-laboratory-diet (SLD) or HFD for 12 weeks, were randomly allocated to: (1) Control: Drinking water; (2) Acute: Drinking water with a gavage of isoleucine (300 mg/kg) prior to the oral-glucose-tolerance-test (OGTT) or gastric-emptying-breath-test (GEBT); (3) Chronic: Drinking water with 1.5% isoleucine, for a further six weeks. At 16 weeks, an OGTT and GEBT was performed and at 17 weeks metabolic monitoring. In SLD- and HFD-mice, there was no difference in body weight, fat mass, and plasma lipid profiles between isoleucine treatment groups. Acute-isoleucine did not improve glucose tolerance in SLD- or HFD-mice. Chronic-isoleucine impaired glucose tolerance in SLD-mice. There was no difference in gastric emptying between any groups. Chronic-isoleucine did not alter energy intake, energy expenditure, or respiratory quotient in SLD- or HFD-mice. In conclusion, chronic isoleucine supplementation may not be an effective treatment for obesity or glucose intolerance.

scholarly journals Development of coronary dysfunction in adult progeny after maternal engineered nanomaterial inhalation during gestation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara B. Fournier ◽  
Vincent Lam ◽  
Michael J. Goedken ◽  
Laura Fabris ◽  
Phoebe A. Stapleton
Keyword(s):  
Cardiovascular Disease ◽  
Body Weight ◽  
Cardiovascular Health ◽  
Metabolic Diseases ◽  
The Body ◽  
Heart Weight ◽  
Myocardial Inflammation ◽  
Adult Offspring ◽  
Sprague Dawley ◽  
Morphological Alterations

AbstractMaternal exposure to environmental contaminants during pregnancy can profoundly influence the risk of developing cardiovascular disease in adult offspring. Our previous studies have demonstrated impaired cardiovascular health, microvascular reactivity, and cardiac function in fetal and young adult progeny after maternal inhalation of nano-sized titanium dioxide (nano-TiO2) aerosols during gestation. The present study was designed to evaluate the development of cardiovascular and metabolic diseases later in adulthood. Pregnant Sprague–Dawley rats were exposed to nano-TiO2 aerosols (~ 10 mg/m3, 134 nm median diameter) for 4 h per day, 5 days per week, beginning on gestational day (GD) 4 and ending on GD 19. Progeny were delivered in-house. Body weight was recorded weekly after birth. After 47 weeks, the body weight of exposed progeny was 9.4% greater compared with controls. Heart weight, mean arterial pressure, and plasma biomarkers of inflammation, dyslipidemia, and glycemic control were recorded at 3, 9 and 12 months of age, with no significant adaptations. While no clinical risk factors (i.e., hypertension, dyslipidemia, or systemic inflammation) emerged pertaining to the development of cardiovascular disease, we identified impaired endothelium-dependent and -independent arteriolar dysfunction and cardiac morphological alterations consistent with myocardial inflammation, degeneration, and necrosis in exposed progeny at 12 months. In conclusion, maternal inhalation of nano-TiO2 aerosols during gestation may promote the development of coronary disease in adult offspring.

scholarly journals Glucose-dependent insulinotropic polypeptide is required for moderate high-fat diet- but not high-carbohydrate diet-induced weight gain

2018 ◽  
Vol 314 (6) ◽  
pp. E572-E583 ◽  
Author(s):  
Ryuya Maekawa ◽  
Hidetada Ogata ◽  
Masatoshi Murase ◽  
Norio Harada ◽  
Kazuyo Suzuki ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
Weight Gain ◽  
Glucose Tolerance ◽  
Body Weight Gain ◽  
Isolated Islets ◽  
Oral Glucose ◽  
High Fat ◽  
High Carbohydrate ◽  
Glucose Tolerance Tests

Both high-fat (HFD) and high-carbohydrate (ST) diets are known to induce weight gain. Glucose-dependent insulinotropic polypeptide (GIP) is secreted mainly from intestinal K cells upon stimuli by nutrients such as fat and glucose, and it potentiates glucose-induced insulin secretion. GIP is well known to contribute to HFD-induced obesity. In this study, we analyzed the effect of ST feeding on GIP secretion and metabolic parameters to explore the role of GIP in ST-induced weight gain. Both wild-type (WT) and GIP receptor deficient ( GiprKO) mice were fed normal chow (NC), ST, or moderate (m)HFD for 22 wk. Body weight was measured, and then glucose tolerance tests were performed. Insulin secretion from isolated islets also was analyzed. WT mice fed ST or mHFD displayed weight gain concomitant with increased plasma GIP levels compared with WT mice fed NC. WT mice fed mHFD showed improved glucose tolerance due to enhanced insulin secretion during oral glucose tolerance tests compared with WT mice fed NC or ST. GiprKO mice fed mHFD did not display weight gain. On the other hand, GiprKO mice fed ST showed weight gain and did not display obvious glucose intolerance. Glucose-induced insulin secretion was enhanced during intraperitoneal glucose tolerance tests and from isolated islets in both WT and GiprKO mice fed ST compared with those fed NC. In conclusion, enhanced GIP secretion induced by mHFD-feeding contributes to increased insulin secretion and body weight gain, whereas GIP is marginally involved in weight gain induced by ST-feeding.

scholarly journals Orexigenic response to tail pinch: role of brain NPY1 and corticotropin releasing factor receptors

2014 ◽  
Vol 306 (3) ◽  
pp. R164-R174 ◽  
Author(s):  
Miriam Goebel-Stengel ◽  
Andreas Stengel ◽  
Lixin Wang ◽  
Yvette Taché
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Body Weight Gain ◽  
The Body ◽  
Corticotropin Releasing Factor ◽  
Sprague Dawley ◽  
Tail Pinch ◽  
Acute Response

Tail pinch stimulates food intake in rats. We investigated brain mechanisms of this response and the influence of repeated exposure. Sprague-Dawley rats received acute (5 min) or repeated (5 min/day for 14 days) tail pinch using a padded clip. Acute tail pinch increased 5-min food intake compared with control (0.92 ± 0.2 vs. 0.03 ± 0.01 g, P < 0.01). This response was inhibited by 76% by intracerebroventricular injection of BIBP-3226, a neuropeptide Y1 (NPY1) receptor antagonist, increased by 48% by astressin-B, a corticotropin-releasing factor (CRF) receptor antagonist, and not modified by S-406-028, a somatostatin subtype 2 antagonist. After the 5-min tail pinch without food, blood glucose rose by 21% ( P < 0.01) while changes in plasma acyl ghrelin (+41%) and adrenocorticotropic hormone (+37%) were not significant. Two tail pinches (45 min apart) activate pontine and hindbrain catecholaminergic and hypothalamic paraventricular CRF neurons. After 14 days of repeated tail pinch, the 5-min orexigenic response was not significantly different from days 2 to 11 but reduced by 50% thereafter ( P < 0.001). Simultaneously, the 5-min fecal pellet output increased during the last 5 days compared with the first 5 days (+58%, P < 0.05). At day 14, the body weight gain was reduced by 22%, with a 99% inhibition of fat gain and a 25% reduction in lean mass ( P < 0.05). The orexigenic response to acute 5-min tail pinch is likely to involve the activation of brain NPY1 signaling, whereas that of CRF tends to dampen the acute response and may contribute to increased defecation and decreased body weight gain induced by repeated tail pinch.

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