Abstract MP40: Microbiome-associated Metabolites Are Altered In Mouse Models Of Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Cristina M Arenaz ◽  
Gaurav Baranwal ◽  
Bethany L Goodlett ◽  
Joseph M Rutkowski ◽  
Robert C Alaniz ◽  
...  
Keyword(s):  
Mouse Models ◽  
High Performance ◽  
Aromatic Amino Acids ◽  
Therapeutic Interventions ◽  
Beta Oxidation ◽  
Serum Fatty Acid ◽  
High Salt Diet ◽  
Induced Hypertension ◽  
Tryptophan Metabolites ◽  
Fatty Acid Beta Oxidation

Recent studies suggest that the microbiome plays a key role in hypertension and associated inflammation. Microbiota produce metabolites that may lead to activated pro-inflammatory immune cells and contribute to hypertension; however, the altered metabolites in multiple models of hypertension is currently unknown. We hypothesized that there are significant differences in metabolomic profiles between normotensive and hypertensive mice. We utilized two mouse models of hypertension: L-arginine methyl ester hydrochloride (L-NAME)/high salt diet induced hypertension (LSHTN) and angiotensin II induced hypertension (A2HTN). Serum and fecal samples were collected at the end of the treatment period. Ultra-high performance liquid chromatography and tandem mass spectrometry were performed to identify the biochemical composition of each sample. Random Forest Analysis was performed to classify each sample based on similarities and differences in metabolite composition. These procedures were performed by Metabolon, Inc. A total of 1,066 and 1,028 biochemicals were measured in serum and feces, respectively. There were 263 biochemicals in LSHTN serum and 122 biochemicals in A2HTN serum that were statistically different from controls (p≤0.05). There were 298 biochemicals in LSHTN feces and 64 biochemicals in A2HTN feces that were statistically different from controls (p≤0.05). Five biochemical metabolite groups were shown to have significant differences between hypertensive groups and controls: aromatic amino acids, bile acids and sterols, benzoates, fatty acids, and diacylglycerols. Tryptophan metabolites were significantly reduced in the serum of LSHTN mice but not in the serum of A2HTN mice. Serum tyrosine and benzoate metabolites showed varied differences between the two hypertensive groups. Serum fatty acid beta oxidation metabolites were significantly reduced in both hypertensive models but were significantly increased in the feces of mice with LSHTN. In conclusion, this study provided significant analysis of metabolite changes in two hypertension mouse models. Further investigation of the roles these metabolites play in hypertension may lead to targeted therapeutic interventions.

scholarly journals Common Metabolites in Two Different Hypertensive Mouse Models: A Serum and Urine Metabolome Study

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1387
Author(s):  
Gaurav Baranwal ◽  
Rachel Pilla ◽  
Bethany L. Goodlett ◽  
Aja K. Coleman ◽  
Cristina M. Arenaz ◽  
...  
Keyword(s):  
Mouse Models ◽  
Active Role ◽  
Experimental Hypertension ◽  
High Salt Diet ◽  
Salt Diet ◽  
Serum Metabolites ◽  
Gut Dysbiosis ◽  
Induced Hypertension ◽  
Metabolomics Analysis ◽  
Serum And Urine

Recent metabolomics studies have identified a wide array of microbial metabolites and metabolite pathways that are significantly altered in hypertension. However, whether these metabolites play an active role in pathogenesis of hypertension or are altered because of this has yet to be determined. In the current study, we hypothesized that metabolite changes common between hypertension models may unify hypertension’s pathophysiology with respect to metabolites. We utilized two common mouse models of experimental hypertension: L-arginine methyl ester hydrochloride (L-NAME)/high-salt-diet-induced hypertension (LSHTN) and angiotensin II induced hypertension (AHTN). To identify common metabolites that were altered across both models, we performed untargeted global metabolomics analysis in serum and urine and the resulting data were analyzed using MetaboAnalyst software and compared to control mice. A total of 41 serum metabolites were identified as being significantly altered in any hypertensive model compared to the controls. Of these compounds, 14 were commonly changed in both hypertensive groups, with 4 significantly increased and 10 significantly decreased. In the urine, six metabolites were significantly altered in any hypertensive group with respect to the control; however, none of them were common between the hypertensive groups. These findings demonstrate that a modest, but potentially important, number of serum metabolites are commonly altered between experimental hypertension models. Further studies of the newly identified metabolites from this untargeted metabolomics analysis may lead to a greater understanding of the association between gut dysbiosis and hypertension.

Abstract MP42: Metabolomic Study To Identify Common Metabolites In Two Different Mouse Models Of Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Gaurav Baranwal ◽  
RACHEL PILLA ◽  
Bethany Goodlett ◽  
Arul Jayaraman ◽  
Joseph M Rutkowski ◽  
...  
Keyword(s):  
Mouse Models ◽  
American Heart ◽  
Heart Association ◽  
Experimental Hypertension ◽  
High Salt Diet ◽  
Salt Diet ◽  
Serum Metabolites ◽  
Induced Hypertension ◽  
Metabolomic Study

Metabolomic Study to Identify Common Metabolites in Two Different Mouse Models of Hypertension Recent studies have reflected the importance of the body’s microbiome and associated metabolites and their changes in hypertension. In the current study, we hypothesized that metabolite changes common between hypertension models may unify hypertension’s pathophysiology with respect to metabolites. Two different mice models of experimental hypertension were used in the study: (1) L-arginine methyl ester hydrochloride (L-NAME)/High salt diet induced hypertension (LSHTN) and (2) angiotensin II induced hypertension (AHTN). Untargeted global metabolomics analysis in serum and urine samples were performed to identify common metabolites altered across both hypertensive models, and the resulting data were analyzed using MetaboAnalyst software and compared to control mice. A list of metabolites that were altered significantly in both models of hypertension were identified. A total of 41 serum metabolites were identified as being altered significantly in any hypertensive model compared to controls. Of these, however, only 4 were increased significantly, and 10 were decreased significantly in common across both hypertensive groups. In the urine, 6 metabolites were altered significantly in any hypertensive group with respect to control, however, 0 of them were common between the hypertensive groups. These findings demonstrate that a modest, but potentially important, number of serum metabolites are commonly altered between experimental hypertension models. Further studies to understand the role of these identified metabolites may lead to a greater understanding of the association between gut dysbiosis and hypertension. Submitted to American Heart Association Council on Hypertension Scientific Sessions (September 27-29, 2021, Virtual)Abstract#: 21-HBPR-A-578-AHA

Overload proteinuria is followed by salt-sensitive hypertension caused by renal infiltration of immune cells

2002 ◽  
Vol 283 (5) ◽  
pp. F1132-F1141 ◽  
Author(s):  
Violeta Alvarez ◽  
Yasmir Quiroz ◽  
Mayerly Nava ◽  
Héctor Pons ◽  
Bernardo Rodríguez-Iturbe
Keyword(s):  
Interstitial Nephritis ◽  
Renal Damage ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Malondialdehyde Content ◽  
Induced Hypertension ◽  
Salt Sensitive Hypertension ◽  
And Control ◽  
And Oxidative Stress

Recent evidence suggests that salt-sensitive hypertension develops as a consequence of renal infiltration with immunocompetent cells. We investigated whether proteinuria, which is known to induce interstitial nephritis, causes salt-sensitive hypertension. Female Lewis rats received 2 g of BSA intraperitoneally daily for 2 wk. After protein overload (PO), 6 wk of a high-salt diet induced hypertension [systolic blood pressure (SBP) = 156 ± 11.8 mmHg], whereas rats that remained on a normal-salt diet and control rats (without PO) on a high-salt diet were normotensive. Administration of mycophenolate mofetil (20 mg · kg−1 · day−1) during PO resulted in prevention of proteinuria-related interstitial nephritis, reduction of renal angiotensin II-positive cells and oxidative stress (superoxide-positive cells and renal malondialdehyde content), and resistance to the hypertensive effect of the high-salt diet (SBP = 129 ± 12.2 mmHg). The present studies support the participation of renal inflammatory infiltrate in the pathogenesis of salt-sensitive hypertension and provide a direct link between two risk factors of progressive renal damage: proteinuria and hypertension.

scholarly journals The enzymology of mitochondrial fatty acid beta-oxidation and its application to follow-up analysis of positive neonatal screening results

2010 ◽  
Vol 33 (5) ◽  
pp. 479-494 ◽  
Author(s):  
Ronald J. A. Wanders ◽  
Jos P. N. Ruiter ◽  
Lodewijk IJlst ◽  
Hans R. Waterham ◽  
Sander M. Houten
Keyword(s):  
Fatty Acid ◽  
Neonatal Screening ◽  
Beta Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Fatty Acid Beta Oxidation

scholarly journals Animal models of bronchopulmonary dysplasia. The term mouse models

2014 ◽  
Vol 307 (12) ◽  
pp. L936-L947 ◽  
Author(s):  
Jessica Berger ◽  
Vineet Bhandari
Keyword(s):  
Animal Models ◽  
Lung Injury ◽  
Mouse Models ◽  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Invasive Mechanical Ventilation ◽  
Therapeutic Interventions ◽  
Contributing Factors ◽  
Short Term ◽  
Injury Models

The etiology of bronchopulmonary dysplasia (BPD) is multifactorial, with genetics, ante- and postnatal sepsis, invasive mechanical ventilation, and exposure to hyperoxia being well described as contributing factors. Much of what is known about the pathogenesis of BPD is derived from animal models being exposed to the environmental factors noted above. This review will briefly cover the various mouse models of BPD, focusing mainly on the hyperoxia-induced lung injury models. We will also include hypoxia, hypoxia/hyperoxia, inflammation-induced, and transgenic models in room air. Attention to the stage of lung development at the timing of the initiation of the environmental insult and the duration of lung injury is critical to attempt to mimic the human disease pulmonary phenotype, both in the short term and in outcomes extending into childhood, adolescence, and adulthood. The various indexes of alveolar and vascular development as well as pulmonary function including pulmonary hypertension will be highlighted. The advantages (and limitations) of using such approaches will be discussed in the context of understanding the pathogenesis of and targeting therapeutic interventions to ameliorate human BPD.

scholarly journals Oogenesis and lipid metabolism in the deep-sea sponge Phakellia ventilabrum: an histological, lipidomic and transcriptomic approach

2021 ◽  
Author(s):  
Vasiliki Koutsouveli ◽  
David Balgoma ◽  
Antonia Checa ◽  
Mikael Hedeland ◽  
Ana Riesgo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Deep Sea ◽  
Expression Patterns ◽  
Rna Seq ◽  
Beta Oxidation ◽  
Animal Reproduction ◽  
Physiological Processes ◽  
Key Species ◽  
Fatty Acid Beta Oxidation

Abstract Background Sponges contain an astounding diversity of lipids which serve in several biological functions, including yolk formation in their oocytes and the embryos. On animal reproduction, lipids constitute one of the main energy storage forms for the adult and the offspring. The study of lipid metabolism during reproduction can provide information on food-web dynamics and energetic needs of the populations in their habitats, however, there are no studies focusing on the lipid metabolism of sponges during seasonal reproduction. The deep-sea sponge Phakellia ventilabrum (Demospongiae, Bubarida) is a key species of North-Atlantic sponge grounds, but its reproductive biology is not known. In this study, we used histological sections, lipidome profiling (UHPLC-MS), and transcriptomic analysis (RNA-seq) with goal to i. assess the reproductive strategy and seasonality of this species, ii. examine the relative changes in the lipidome signal, and the gene expression patterns (RNA-seq) of enzymes participating in lipid metabolism in female specimens during gametogenesis.Results P. ventilabrum is an oviparous and most certainly gonochoristic species, reproducing in May and September in the different studied areas. Half of specimens were reproducing, generating two to five oocytes per mm2. Oocytes accumulated both protein and lipid droplets. As oogenesis progressed, the signal of most of the unsaturated and monounsaturated triacylglycerides increased, as well as of few other phospholipids. Most of the other lipids and especially those with > 3 unsaturations showed a decrease in signal during the oocyte maturation. In parallel, we detected upregulated genes in female tissues related to triacylglyceride biosynthesis and others related to fatty acid beta-oxidation.Conclusions Triacylglycerides are probably the main type of lipid forming the yolk since this lipid category has the most marked changes, while some other phospholipids may also have a role in oogenesis. In parallel, other lipid categories were oxidized, leading to fatty acid beta-oxidation to cover the energy requirements of female individuals during oogenesis. Variations in the signal of most lipids between the different locations and months suggest that sponges, apart from their own mechanisms of lipid biosynthesis, exploit the food availability in their surroundings to cover the energetic demands in their physiological processes.

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