Deficiency of Angiotensinogen in Hepatocytes Markedly Decreases Blood Pressure in Lean and Obese Male Mice

Angiotensin-1-7 (Ang-(1-7)) counteracts angiotensin II through effects at Mas receptors (MasR). We demonstrated that sexual dimorphism of obesity-hypertension was associated with dysregulated production of Ang-(1-7). However, the role of MasR in sexual dimorphism of obesity-hypertension has not been examined. MasR deficient mice have also been reported to exhibit deficits in cardiac function. In this study, we hypothesized that deficiency of the MasR would differentially regulate obesity-hypertension in male versus ( vs ) female mice. In addition, we quantified effects of MasR deficiency on cardiac function in obese male mice. Male and female MasR +/+ and -/- mice were fed a low fat (LF, 10%kcal) or high fat (HF, 60% kcal) diet for 16 weeks, and blood pressure was quantified by radiotelemetry. As demonstrated previously, male MasR +/+ mice (24 hr diastolic blood pressure, DBP: LF, 90 ± 3; HF, 96 ± 2 mmHg; P<0.05), but not females (LF, 85 ± 1; HF, 85 ± 2 mmHg), developed hypertension in response to HF feeding. MasR deficiency converted female HF-fed mice to an obesity-hypertension phenotype (DBP: 92 ± 1 mmHg; P<0.05). Surprisingly, male HF-fed MasR -/- mice exhibited reduced DBP compared to HF-fed MasR +/+ males (90 ± 1 vs 96 ± 2 mmHg; P<0.05). To define mechanisms for reductions in DBP of HF-fed male MasR -/- mice, we performed cardiac magnetic resonance (CMR) imaging in both genotypes at 1 month of HF feeding. MasR -/- mice had significantly reduced ejection fraction (EF) compared to MasR +/+ mice at baseline (51.4 ± 2.5 vs 59.3 ± 2.1%; P<0.05) and after one month of HF-feeding (49.8 ± 2.4 vs 52.6 ± 1.9%; P<0.05). Further, CMR imaging demonstrated a thickening of the ventricle wall in MasR -/- mice with 1 month of HF-feeding. MasR +/+ , but not MasR -/- mice, exhibited diet-induced reductions in EF (by 16%; P<0.05) at 1 month of HF feeding, which were reversed by infusion of Ang-(1-7). These results demonstrate that MasR contributes to sexual dimorphism of obesity-hypertension. Ang-(1-7) protects females from obesity-hypertension through the MasR. In contrast, reductions in DBP in obese male mice with MasR deficiency may arise from deficits in cardiac function. These results suggest that MasR agonists may be effective therapies for obesity-associated cardiovascular conditions.

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Determining the Effects of Combined Liraglutide and Phentermine on Metabolic Parameters, Blood Pressure, and Heart Rate in Lean and Obese Male Mice

Diabetes ◽

10.2337/db18-1149 ◽

2019 ◽

Vol 68 (4) ◽

pp. 683-695 ◽

Cited By ~ 2

Author(s):

Stephanie E. Simonds ◽

Jack T. Pryor ◽

Frank H. Koegler ◽

Alberte S. Buch-Rasmussen ◽

Lauren E. Kelly ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Metabolic Parameters ◽

Male Mice ◽

Obese Male

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Exacerbated Blood Pressure Response to Sensory Neurons Stimulation in Fat Increases the Renal Sympathetic Outflow in Obese Male Mice Exposed to Early Life Stress

The FASEB Journal ◽

10.1096/fasebj.2021.35.s1.02312 ◽

2021 ◽

Vol 35 (S1) ◽

Author(s):

Carolina Dalmasso ◽

Jacqueline Leachman ◽

Nermin Ahmed ◽

Sundus Ghuneim ◽

Jeffrey Osborn ◽

...

Keyword(s):

Blood Pressure ◽

Sensory Neurons ◽

Life Stress ◽

Early Life ◽

Blood Pressure Response ◽

Early Life Stress ◽

Sympathetic Outflow ◽

Male Mice ◽

Obese Male ◽

Renal Sympathetic

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Selective Afferent Denervation in Epididymal White Adipose Tissue Reduces Blood Pressure in Obese Male Mice Exposed to Early Life Stress

The FASEB Journal ◽

10.1096/fasebj.2021.35.s1.02781 ◽

2021 ◽

Vol 35 (S1) ◽

Author(s):

Carolina Dalmasso ◽

Jacqueline Leachman ◽

Nermin Ahmed ◽

Sundus Ghuneim ◽

Analia Loria

Keyword(s):

Blood Pressure ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Male Mice ◽

Epididymal White Adipose Tissue ◽

Obese Male

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FERTILITY IN GOLDTHIOGLUCOSE OBESE MALE MICE AND INFERTILITY IN BROWN HEREDITARY OBESE MALE MICE BEFORE AND DURING FORCED EXERCISE

Acta Endocrinologica ◽

10.1530/acta.0.067s233 ◽

1971 ◽

Vol 68 (1_Supplb) ◽

pp. S233

Author(s):

Niels Einer-Jensen

Keyword(s):

Male Mice ◽

Obese Male

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

Hypertension ◽

10.1161/hyp.64.suppl_1.620 ◽

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.

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Abstract 064: 20-HETE Contributes to Vasoconstriction of Renal Microvessels and Sodium Retention in Cyp4a14-/- Mice, a Model of 20-HETE Dependent Hypertension

Hypertension ◽

10.1161/hyp.66.suppl_1.064 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Ankit Gilani ◽

Varunkumar Pandey ◽

Joseph Zullo ◽

Priyanka Mishra ◽

John R Falck ◽

...

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Isotonic Saline ◽

Urinary Sodium Excretion ◽

Water Soluble ◽

Arachidonic Acid Metabolite ◽

Male Mice ◽

Kidney Weight ◽

Doppler Flowmetry ◽

In The Wild

20-HETE (20-Hydroxyeicosatetraenoic acid), is a cytochrome P450 (CYP) 4A-derived arachidonic acid metabolite. 20-HETE has been linked to both pro-hypertensive (via increased vasoconstriction, vascular remodeling and vascular injury of renal microvessels) and anti-hypertensive (inhibiting ion transport in the distal nephron) functions. In this study we examined the effect of 20-SOLA (2,5,8,11,14,17-hexaoxanonadecan-19-yl-20-hydroxyeicosa-6(Z),15(Z)-dienoate), a water soluble antagonist of the actions of 20-HETE on renal hemodynamics and sodium (Na) excretion in Cyp4a14 knockout (CYP4a14-/-) male mice. The CYP4a14-/- male mice display hypertension accompanied by increased vascular 20-HETE levels. Administration of 20-SOLA (10mg/kg/day in drinking water) normalized blood pressure (BP) in male Cyp4a14-/- mice at day 10 of treatment (124±1 vs. 153±2 mmHg in untreated male Cyp4a14-/- mice; p<0.05). The normalization of blood pressure was accompanied by transient increase in the urinary sodium excretion in the Cyp4a14-/- male mice (8.3±0.7 vs. 5.8±0.5 μmol/g body weight/day; p<0.05). Importantly, 20-SOLA increased glomerular filtration rate (GFR) of Cyp4a14-/- mice (2.38±0.05 vs. 1.88±0.18 μL/min/mg kidney weight, p<0.05) as opposed to no changes observed in the wild type (WT: (2.26±0.18 vs. 2.33±0.20μL/min/mg kidney weight). Evaluation of the renal blood flow (RBF) by laser Doppler flowmetry showed that treatment with 20-SOLA increased the RBF in Cyp4a14-/- mice by 12.3±4%, which remained unaltered in the WT. Additionally, the pressure-induced myogenic tone of isolated preglomerular microvessels was significantly elevated in Cyp4a14-/- mice; 20-SOLA treatment prevented the increase in myogenic responses. The natriuretic response to an isotonic saline loading challenge (10% of body weight, IP) was significantly attenuated in the Cyp4a14-/- mice as compared to the WT (35.5±2.8 vs. 57.4±8.3 percentage of Na load, p<0.05); this was corrected by 20-SOLA (61.7±5.7 percentage of Na load, p<0.05). These results confirm that 20-SOLA normalizes blood pressure of Cyp4a14-/- male mice and demonstrates that this is associated with increases in GFR, RBF and natriuresis.

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Anti-Obesity Effects of Combined Cornus officinalis and Ribes fasciculatum Extract in High-Fat Diet-Induced Obese Male Mice

Animals ◽

10.3390/ani11113187 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3187

Author(s):

Eunkuk Park ◽

Chang-Gun Lee ◽

Hyoju Jeon ◽

Hyesoo Jeong ◽

Subin Yeo ◽

...

Keyword(s):

High Fat Diet ◽

Insulin Action ◽

Normal Diet ◽

Male Mice ◽

Impaired Glucose Metabolism ◽

High Fat ◽

Beneficial Effects ◽

Cornus Officinalis ◽

Treatment And Prevention ◽

Obese Male

Medicinal plants are widely used as supplements for the treatment of various diseases because of their few side-effects. Here, we examined the anti-obesity effects of a mixture extract of Cornus officinalis and Ribes fasciculatum (CR) in high-fat diet (HFD)-induced obese male mice. Four week old male C57BL/6J mice were fed a normal diet (ND) or 60% high-fat diet (HFD) with different concentrations of CR extracts (75, 150, and 300 mg/kg/day) by oral administration for 12 weeks. CR extract administration prevented HFD-induced weight gain, hepatic steatosis, and adipocyte enlargement through the downregulation of adipogenesis-associated genes in obese male mice. In addition, CR administration improved the impaired glucose metabolism, insulin action, biochemical obesity parameters, and metabolic profiles in HFD-induced male mice. Consequently, the CR extract exhibited beneficial effects on HFD-induced systemic metabolic challenges. Taken together, our findings suggest that CR extract may be a potent therapeutic supplement for the treatment and prevention of obesity.

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