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Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat

Body fat distribution contributes to obesity-related metabolic and cardiovascular disorders. Visceral fat is more detrimental than subcutaneous fat. However, the mechanisms underlying visceral fat-mediated cardiometabolic dysregulation are not completely understood. Localized increases in expression...

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Autores principales: Zhang, Yuebo, Somers, Kiran R., Becari, Christiane, Polonis, Katarzyna, Pfeifer, Michaela A., Allen, Alina M., Kellogg, Todd A., Covassin, Naima, Singh, Prachi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191467/
https://www.ncbi.nlm.nih.gov/pubmed/30364113
http://dx.doi.org/10.3389/fphys.2018.01370
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author Zhang, Yuebo
Somers, Kiran R.
Becari, Christiane
Polonis, Katarzyna
Pfeifer, Michaela A.
Allen, Alina M.
Kellogg, Todd A.
Covassin, Naima
Singh, Prachi
author_facet Zhang, Yuebo
Somers, Kiran R.
Becari, Christiane
Polonis, Katarzyna
Pfeifer, Michaela A.
Allen, Alina M.
Kellogg, Todd A.
Covassin, Naima
Singh, Prachi
author_sort Zhang, Yuebo
collection PubMed
description Body fat distribution contributes to obesity-related metabolic and cardiovascular disorders. Visceral fat is more detrimental than subcutaneous fat. However, the mechanisms underlying visceral fat-mediated cardiometabolic dysregulation are not completely understood. Localized increases in expression of the renin angiotensin system (RAS) in adipose tissue (AT) may be implicated. We therefore investigated mRNA and protein expression of RAS components in visceral versus subcutaneous AT using paired samples from individuals undergoing surgery (N = 20, body mass index: 45.6 ± 6.2 kg/m(2), and age: 44.6 ± 9.1 years). We also examined RAS-related proteins in AT obtained from individuals on renin angiotensin aldosterone system (RAAS) targeted drugs (N = 10, body mass index: 47.2 ± 9.3 kg/m(2), and age: 53.3 ± 10.1 years). Comparison of protein expression between subcutaneous and visceral AT samples showed an increase in renin (p = 0.004) and no change in angiotensinogen (p = 0.987) expression in visceral AT. Among proteins involved in angiotensin peptide generation, angiotensin converting enzyme (p = 0.02) was increased in subcutaneous AT while chymase (p = 0.001) and angiotensin converting enzyme-2 (p = 0.001) were elevated in visceral fat. Furthermore, visceral fat expression of angiotensin II type-2 receptor (p = 0.007) and angiotensin II type-1 receptor (p = 0.031) was higher, and MAS receptor (p < 0.001) was lower. Phosphorylated-p53 (p = 0.147), AT fibrosis (p = 0.138) and average adipocyte size (p = 0.846) were similar in the two depots. Nonetheless, visceral AT showed increased mRNA expression of inflammatory (TNFα, p < 0.001; IL-6, p = 0.001) and oxidative stress markers (NOX2, p = 0.038; NOX4, p < 0.001). Of note, mRNA and protein expression of RAS components did not differ between subjects taking or not taking RAAS related drugs. In summary, several RAS related proteins are differentially expressed in subcutaneous versus visceral AT. This differential expression may not alter AngII but likely increases Ang1-7 generation in visceral fat. These potential differences in active angiotensin peptides and receptor expression in the two depots suggest that localized RAS may not be involved in differences in visceral vs subcutaneous AT function in obese individuals. Our findings do not support a role for localized RAS differences in visceral fat-mediated development of cardiovascular and metabolic pathology.
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spelling pubmed-61914672018-10-24 Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat Zhang, Yuebo Somers, Kiran R. Becari, Christiane Polonis, Katarzyna Pfeifer, Michaela A. Allen, Alina M. Kellogg, Todd A. Covassin, Naima Singh, Prachi Front Physiol Physiology Body fat distribution contributes to obesity-related metabolic and cardiovascular disorders. Visceral fat is more detrimental than subcutaneous fat. However, the mechanisms underlying visceral fat-mediated cardiometabolic dysregulation are not completely understood. Localized increases in expression of the renin angiotensin system (RAS) in adipose tissue (AT) may be implicated. We therefore investigated mRNA and protein expression of RAS components in visceral versus subcutaneous AT using paired samples from individuals undergoing surgery (N = 20, body mass index: 45.6 ± 6.2 kg/m(2), and age: 44.6 ± 9.1 years). We also examined RAS-related proteins in AT obtained from individuals on renin angiotensin aldosterone system (RAAS) targeted drugs (N = 10, body mass index: 47.2 ± 9.3 kg/m(2), and age: 53.3 ± 10.1 years). Comparison of protein expression between subcutaneous and visceral AT samples showed an increase in renin (p = 0.004) and no change in angiotensinogen (p = 0.987) expression in visceral AT. Among proteins involved in angiotensin peptide generation, angiotensin converting enzyme (p = 0.02) was increased in subcutaneous AT while chymase (p = 0.001) and angiotensin converting enzyme-2 (p = 0.001) were elevated in visceral fat. Furthermore, visceral fat expression of angiotensin II type-2 receptor (p = 0.007) and angiotensin II type-1 receptor (p = 0.031) was higher, and MAS receptor (p < 0.001) was lower. Phosphorylated-p53 (p = 0.147), AT fibrosis (p = 0.138) and average adipocyte size (p = 0.846) were similar in the two depots. Nonetheless, visceral AT showed increased mRNA expression of inflammatory (TNFα, p < 0.001; IL-6, p = 0.001) and oxidative stress markers (NOX2, p = 0.038; NOX4, p < 0.001). Of note, mRNA and protein expression of RAS components did not differ between subjects taking or not taking RAAS related drugs. In summary, several RAS related proteins are differentially expressed in subcutaneous versus visceral AT. This differential expression may not alter AngII but likely increases Ang1-7 generation in visceral fat. These potential differences in active angiotensin peptides and receptor expression in the two depots suggest that localized RAS may not be involved in differences in visceral vs subcutaneous AT function in obese individuals. Our findings do not support a role for localized RAS differences in visceral fat-mediated development of cardiovascular and metabolic pathology. Frontiers Media S.A. 2018-10-10 /pmc/articles/PMC6191467/ /pubmed/30364113 http://dx.doi.org/10.3389/fphys.2018.01370 Text en Copyright © 2018 Zhang, Somers, Becari, Polonis, Pfeifer, Allen, Kellogg, Covassin and Singh. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Zhang, Yuebo
Somers, Kiran R.
Becari, Christiane
Polonis, Katarzyna
Pfeifer, Michaela A.
Allen, Alina M.
Kellogg, Todd A.
Covassin, Naima
Singh, Prachi
Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat
title Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat
title_full Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat
title_fullStr Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat
title_full_unstemmed Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat
title_short Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat
title_sort comparative expression of renin-angiotensin pathway proteins in visceral versus subcutaneous fat
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191467/
https://www.ncbi.nlm.nih.gov/pubmed/30364113
http://dx.doi.org/10.3389/fphys.2018.01370
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