Abstract 620: Development Of A New Mouse Model Exhibiting A Specific Deficiency Of Prorenin Renin Receptor In Adipocytes.

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Frederique B Yiannikouris ◽  
Genevieve Nguyen
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Mouse Model ◽  
Preliminary Data ◽  
The Body ◽  
Chow Diet ◽  
Slight Reduction ◽  
Male Mice ◽  
Exon 2 ◽  
Adipose Tissue Stromal Cells

Objectives: Recent studies demonstrated that the prorenin renin receptor (PRR) is present in adipose tissue. In adipose tissue stromal cells, PRR has the ability to bind renin and prorenin and contributes to the generation of angiotensinI (AngI). However, the contribution of adipocyte PRR to the generation of the vasoactive peptide, AngII and therefore to the regulation of blood pressure in physiological condition is unknown. The purpose of this study was to develop and characterize a new mouse model with adipocyte-specific PRR deficiency and define the role of adipose PRR in normal physiology. Methods and results: Female mice with 2 loxP sites flanking exon 2 of the PRR gene (floxed alleles, PRRfl/fl) were bred with aP2-Cre or with Adi-Cre male mice. Since PRR is located in the X chromosome, the male mice generated from the breeding were homozygotes for the deletion (PRRaP2 and PRRAdi). From the breeding, 5 PRRfl/fl, 2 PRRaP2 and 5 PRRAdi male mice were generated suggesting that the deletion of PRR in adipocyte was not lethal. Mice were fed on chow diet during 20 weeks. The body weight, the fat, lean mass and the blood pressure were quantified. Preliminary data suggest that the body weights (BW) were slightly decreased in PRRaP2 and PRRAdi compared to PRRfl/fl (PRRfl/fl: 29±1g; PRRaP2: 25±5g; PRRAdi: 28±1g). The slight reduction in BW was attributed to a reduction in fat mass (PRRfl/fl: 4.8±0.9g; PRRaP2: 3.8±1.8g; PRRAdi: 1.9±0.4g). Blood pressure was measured by plethysmography and by radiotelemetry. Preliminary data demonstrated that under physiological conditions, the SBP was not changed in PRRaP2 male mice compared to PRRfl/fl mice (plethysmography: PRRfl/fl: 108±1 mmHg; PRRaP2: 99±7 mmHg; radiotelemetry: PRRfl/fl: 129±2 mmHg; PRRaP2: 128±6 mmHg). The SBP of PRRAdi is currently under investigation. Conclusions: These results demonstrate the viability of mice with specific adipocyte deficiency of PRR. Future studies will define the effects of adipocyte PRR deficiency on obesity-induced hypertension.

scholarly journals Anti-Obesity Effects of Collagen Peptide Derived from Skate (Raja kenojei) Skin Through Regulation of Lipid Metabolism

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 306 ◽  
Author(s):  
Minji Woo ◽  
Yeong Song ◽  
Keon-Hee Kang ◽  
Jeong Noh
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Protein Expression ◽  
The Body ◽  
Chow Diet ◽  
Dependent Manner ◽  
Hepatic Lipid ◽  
Collagen Peptide

This study investigated the anti-obesity effects of collagen peptide derived from skate skin on lipid metabolism in high-fat diet (HFD)-fed mice. All C57BL6/J male mice were fed a HFD with 60% kcal fat except for mice in the normal group which were fed a chow diet. The collagen-fed groups received collagen peptide (1050 Da) orally (100, 200, or 300 mg/kg body weight per day) by gavage, whereas the normal and control groups were given water (n = 9 per group). The body weight gain and visceral adipose tissue weight were lower in the collagen-fed groups than in the control group (p < 0.05). Plasma and hepatic lipid levels were significantly reduced by downregulating the hepatic protein expression levels for fatty acid synthesis (sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC)) and cholesterol synthesis (SREBP-2 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)) and upregulating those for β-oxidation (peroxisome proliferator-activated receptor alpha (PPAR-α) and carnitine palmitoyltransferase 1 (CPT1)) and synthesis of bile acid (cytochrome P450 family 7 subfamily A member 1 (CYP7A1)) (p < 0.05). In the collagen-fed groups, the hepatic protein expression level of phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK) and plasma adiponectin levels were higher, and the leptin level was lower (p < 0.05). Histological analysis revealed that collagen treatment suppressed hepatic lipid accumulation and reduced the lipid droplet size in the adipose tissue. These effects were increased in a dose-dependent manner. The findings indicated that skate collagen peptide has anti-obesity effects through suppression of fat accumulation and regulation of lipid metabolism.

scholarly journals Pharmacological myeloperoxidase (MPO) inhibition in an obese/hypertensive mouse model attenuates obesity and liver damage, but not cardiac remodeling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Arnold Piek ◽  
Debby P. Y. Koonen ◽  
Elisabeth-Maria Schouten ◽  
Eva L. Lindtstedt ◽  
Erik Michaëlsson ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mouse Model ◽  
The Body ◽  
Low Grade ◽  
Protective Effects ◽  
Positive Effects ◽  
Low Fat Diet ◽  
Multiple Organs ◽  
Cardiac Phenotype ◽  
Obesity Hypertension

AbstractLifestyle factors are important drivers of chronic diseases, including cardiovascular syndromes, with low grade inflammation as a central player. Attenuating myeloperoxidase (MPO) activity, an inflammatory enzyme associated with obesity, hypertension and heart failure, could have protective effects on multiple organs. Herein, the effects of the novel oral available MPO inhibitor AZM198 were studied in an obese/hypertensive mouse model which displays a cardiac phenotype. Eight week old male C57BL6/J mice received 16 weeks of high fat diet (HFD) combined with angiotensin II (AngII) infusion during the last 4 weeks, with low fat diet and saline infusion as control. Treated animals showed therapeutic AZM198 levels (2.1 µM), corresponding to 95% MPO inhibition. AZM198 reduced elevated circulating MPO levels in HFD/AngII mice to normal values. Independent of food intake, bodyweight increase and fat accumulation were attenuated by AZM198, alongside with reduced visceral adipose tissue (VAT) inflammation and attenuated severity of nonalcoholic steatohepatitis. The HFD/AngII perturbation caused impaired cardiac relaxation and contraction, and increased cardiac hypertrophy and fibrosis. AZM198 treatment did, however, not improve these cardiac parameters. Thus, AZM198 had positive effects on the main lipid controlling tissues in the body, namely adipose tissue and liver. This did, however, not directly result in improved cardiac function.

scholarly journals Taurine Stimulates Thermoregulatory Genes in Brown Fat Tissue and Muscle without an Influence on Inguinal White Fat Tissue in a High-Fat Diet-Induced Obese Mouse Model

Foods ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 688 ◽  
Author(s):  
Kyoung Soo Kim ◽  
Hari Madhuri Doss ◽  
Hee-Jin Kim ◽  
Hyung-In Yang
Keyword(s):  
Adipose Tissue ◽  
Mouse Model ◽  
High Fat Diet ◽  
Fat Deposition ◽  
Chow Diet ◽  
Fat Tissue ◽  
High Fat ◽  
Taurine Supplementation ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

This study was conducted to investigate if taurine supplementation stimulates the induction of thermogenic genes in fat tissues and muscles and decipher the mechanism by which taurine exerts its anti-obesity effect in a mildly obese ICR (CD-1®) mouse model. Three groups of ICR mice were fed a normal chow diet, a high-fat diet (HFD), or HFD supplemented with 2% taurine in drinking water for 28 weeks. The expression profiles of various genes were analyzed by real time PCR in interscapular brown adipose tissue (BAT), inguinal white adipose tissue (iWAT), and the quadriceps muscles of the experimental groups. Genes that are known to regulate thermogenesis like PGC-1α, UCP-1, Cox7a1, Cox8b, CIDE-A, and β1-, β2-, and β3-adrenergic receptors (β-ARs) were found to be differentially expressed in the three tissues. These genes were expressed at a very low level in iWAT as compared to BAT and muscle. Whereas, HFD increased the expression of these genes. Taurine supplementation stimulated the expression of UCP-1, Cox7a1, and Cox8b in BAT and only Cox7a1 in muscle, while there was a decrease in iWAT. In contrast, fat deposition-related genes, monoamine oxidases (MAO)-A, and -B, and lipin-1, were decreased by taurine supplementation only in iWAT and not in BAT or muscle. In conclusion, the potential anti-obesity effects of taurine may be partly due to upregulated thermogenesis in BAT, energy metabolism of muscle, and downregulated fat deposition in iWAT.

Protective effect of artificially induced ‘hibernation’ against lethal doses of whole body x-irradiation in CF1 male mice

1959 ◽  
Vol 196 (6) ◽  
pp. 1211-1213 ◽  
Author(s):  
Sondra M. Kuskin ◽  
S. C. Wang ◽  
Roberts Rugh
Keyword(s):  
Protective Action ◽  
Lethal Dose ◽  
Lethal Effect ◽  
The Body ◽  
Whole Body ◽  
Protective Mechanism ◽  
Slight Reduction ◽  
Male Mice ◽  
Degree Of Protection ◽  
X Irradiation

Hypothermia induced by the use of neuroplegic drugs such as Hydergine, chlorpromazine or promethazine, followed by refrigeration, does not significantly enhance the protective action afforded by refrigeration alone against the lethal dose of whole body x-irradiation in CF1 male mice. The neuroplegic drugs, without refrigeration, provide a slight degree of protection, probably due to the slight reduction in the body temperature. It appears that the action of hypothermia as a protective mechanism depends not on depression of metabolism alone, but on a general depression of bodily processes. Urethane, in conjunction with refrigeration, appears to augment the lethal effect of x-irradiation in the CF1 strain of male mice.

scholarly journals Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice

2012 ◽  
Vol 302 (2) ◽  
pp. R244-R251 ◽  
Author(s):  
Frederique Yiannikouris ◽  
Michael Karounos ◽  
Richard Charnigo ◽  
Victoria L. English ◽  
Debra L. Rateri ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Adipose Tissue ◽  
Blood Pressure Control ◽  
Fat Mass ◽  
Plasma Concentrations ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Fatty Acid Binding ◽  
Exon 2

Previous studies demonstrated that overexpression of angiotensinogen (AGT) in adipose tissue increased blood pressure. However, the contribution of endogenous AGT in adipocytes to the systemic renin-angiotensin system (RAS) and blood pressure control is undefined. To define a role of adipocyte-derived AGT, mice with loxP sites flanking exon 2 of the AGT gene ( Agt fl/fl) were bred to transgenic mice expressing Cre recombinase under the control of an adipocyte fatty acid-binding protein 4 promoter (aP2) promoter to generate mice with adipocyte AGT deficiency ( Agt aP2). AGT mRNA abundance in adipose tissue and AGT secretion from adipocytes were reduced markedly in adipose tissues of Agt aP2 mice. To determine the contribution of adipocyte-derived AGT to the systemic RAS and blood pressure control, mice were fed normal laboratory diet for 2 or 12 mo. In males and females of each genotype, body weight and fat mass increased with age. However, there was no effect of adipocyte AGT deficiency on body weight, fat mass, or adipocyte size. At 2 and 12 mo of age, mice with deficiency of AGT in adipocytes had reduced plasma concentrations of AGT (by 24–28%) compared with controls. Moreover, mice lacking AGT in adipocytes exhibited reduced systolic blood pressures compared with controls ( Agt fl/fl, 117 ± 2; Agt aP2, 110 ± 2 mmHg; P < 0.05). These results demonstrate that adipocyte-derived AGT contributes to the systemic RAS and blood pressure control.

scholarly journals Sex-Specific Difference in Adipose Tissue and Blood Pressure in a New Mouse Model Expressing Human Soluble Prorenin Receptor in Adipocytes

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 56-56
Author(s):  
Kellea Nichols ◽  
Audrey Poupeau ◽  
Eva Gatineau ◽  
Gertrude Arthur ◽  
Ming Gong ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Mouse Model ◽  
Fat Mass ◽  
Lean Mass ◽  
Soluble Form ◽  
Male Mice ◽  
Female Mice ◽  
Prorenin Receptor ◽  
Body Weights

Abstract Objectives Sex differences exist in obesity associated with cardiovascular disease; however, underlying mechanisms are not completely understood. Previous studies from our laboratory demonstrated that the prorenin receptor (PRR) and its soluble form (sPRR) contribute to adipogenesis and blood pressure control. The present study aimed to determine whether adipose-sPRR stimulated obesity is associated with hypertension and whether it is sex-dependent. Methods Transgenic mice on the C57BL/6 J background were generated expressing the human form of the soluble prorenin receptor (HsPRR) in a Cre-inducible manner. Male mice expressing Cre recombinase under the control of the adiponectin promotor were bred to heterozygote HsPRR/+ female mice to generate mice over-secreting sPRR (adi-HsPRR) and control littermate mice (CTL). The secretion of sPRR in the media doubled in primary adipocytes of adi-HsPRR mice compared to control mice (sPRR. CTL: 3729 ± 805 pg/ml; adi-HsPRR: 6170 ± 1237 pg/ml, P &lt; 0.05) validating the mouse model. Male (CTL = 4; adi-HsPRR = 8) and female mice (CTL = 10; adi-HsPRR = 10) were fed a low-fat (LF) diet or a high-fat diet (HF) for 20 weeks. Body weight was assessed weekly and EchoMRI was examined monthly. Results After 20 weeks on LF diet, adi-HsPRR male mice gained significantly more weight than CTL male mice (CTL: 25.1 ± 0.8 g; adi-HsPRR: 29.0 ± 0.8 g P &lt; 0.05), whereas no significant differences in body weights were observed in female mice. The body composition revealed a significant increase of fat mass, specifically in the epidydimal fat (CTL: 0.35 ± 0.04 g; adi-HsPRR: 0.61 ± 0.07 g, P &lt; 0.05), and lean mass of HsPRR male mice compared to CTL male mice. In contrast, female mice exhibited similar body weights (CTL: 20.6 ± 0.3 g; adi-HsPRR: 20.4 ± 0.4 g) and there was no differences of fat mass or lean mass between CTL and adi-HsPRR female mice. The sex-specific mechanism of sPRR on adipogenesis and blood pressure (by radiotelemetry) with LF and HF diet is currently under investigation. Conclusions Overall, sPRR stimulated body weight gain and fat mass expansion in male mice but not in female mice suggesting that female mice are protected from sPRR induced-hypertrophic effect. Funding Sources R01_HL142969–01 Yiannikouris, PI 07/15/2018–06/30/2022 NIH/NHLBI Title: The role of soluble prorenin receptor in hypertension associated with obesity Role: Ph.D Graduate Student.

scholarly journals Estrogen modulation of baroreflex function in conscious mice

2003 ◽  
Vol 284 (4) ◽  
pp. R983-R989 ◽  
Author(s):  
Jaya Pamidimukkala ◽  
Julia A. Taylor ◽  
Wade V. Welshons ◽  
Dennis B. Lubahn ◽  
Meredith Hay
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mouse Model ◽  
Sodium Nitroprusside ◽  
Autonomic Function ◽  
Ang Ii ◽  
Male Mice ◽  
Female Mice ◽  
Reflex Bradycardia ◽  
Baroreflex Function

It has been suggested that estrogen modulates baroreflex regulation of autonomic function. The present study evaluated the effects of estrogen on baroreflex regulation of heart rate in response to changes in blood pressure with phenylephrine (PE), ANG II, and sodium nitroprusside (SNP) in a conscious mouse model. Males and ovariectomized females with (OvxE+) and without (OvxE−) estradiol replacement chronically implanted with arterial and venous catheters were used in these studies. The slope of the baroreflex bradycardic responses to PE was significantly facilitated in OvxE+ females (−7.65 ± 1.37) compared with OvxE− females (−4.5 ± 0.4). Likewise, the slope of the baroreflex bradycardic responses to ANG II was significantly facilitated in OvxE+ females (−7.97 ± 1.06) compared with OvxE− females (−4.8 ± 1.6). Reflex tachycardic responses to SNP were comparable in all the groups. Finally, in male mice, the slope of ANG II-induced baroreflex bradycardia (−5.17 ± 0.95) was significantly less than that induced by PE (−8.50 ± 0.92), but this ANG II-mediated attenuation of reflex bradycardia was not observed in the female mice. These data support the hypothesis that estrogen facilitates baroreflex function in female mice and suggest that ANG II-mediated acute blunting of baroreflex regulation of heart rate may be sex dependent.

scholarly journals Epicardial adipose tissue as a marker of visceral obesity and its association with metabolic parameters and remodeling of the left chambers of the heart in young people with abdominal obesity

2019 ◽  
Vol 91 (9) ◽  
pp. 68-76
Author(s):  
N V Blinova ◽  
M O Azimova ◽  
Y V Zhernakova ◽  
E A Zheleznova ◽  
E B Yarovaya ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Waist Circumference ◽  
Abdominal Obesity ◽  
Epicardial Adipose Tissue ◽  
Left Ventricular ◽  
The Body ◽  
Metabolic Parameters ◽  
Lv Mass

Aim: to study the correlation of epicardial adipose tissue (EAT) with metabolic parameters, 24-hours profile of blood pressure (BP) and left ventricular remodeling, with the volume of intraabdominal adipose tissue (IAAT), measured by multislice computed tomography (MSCT) in patients with abdominal obesity and metabolic syndrome. Materials and methods: the study included 80 participants with abdominal obesity (waist circumference > 80 cm in women and >94 cm in men) and without cardiovascular diseases and diabetes. Within this study the following examinations were performed: waist circumference and the body mass index measurement, blood sampling and measurements of lipid levels, uric acid, fasting glucose, insulin, HOMA index, 24-hour ambulatory blood pressure monitoring. Left ventricular (LV) mass index, relative wall thickness, LV mass/height index were estimated from echocardiographic data. EAT volume and IAAT was measured by MSCT. All patients was devided in two groups for analysis: 1 (n=28) - patients with isolated abdominal obesity, without metabolic syndrome, age was 37.5±6.43 years; 2 (n=52) - patients with metabolic syndrome, age - 38.8±5.88 years. The control group 0 included healthy individuals (n=13) without obesity, age was 30.5±5.97 years. Results. A positive correlation was found between the volume of EAT with the level of insulin in the blood (r=0.2937, p

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