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Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity

Western diet-induced obesity is linked to the development of metabolic dysfunctions, including type 2 diabetes and complications that include retinopathy, a leading cause of blindness. Aberrant activation of the inflammasome cascade leads to the progression of obesity-induced pathologies. Our lab sh...

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Autores principales: Atawia, Reem T., Bunch, Katharine L., Fouda, Abdelrahman Y., Lemtalsi, Tahira, Eldahshan, Wael, Xu, Zhimin, Saul, Alan, Elmasry, Khaled, Al-Shabrawey, Mohamed, Caldwell, Ruth B., Caldwell, R. William
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073940/
https://www.ncbi.nlm.nih.gov/pubmed/31979105
http://dx.doi.org/10.3390/jcm9020317
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author Atawia, Reem T.
Bunch, Katharine L.
Fouda, Abdelrahman Y.
Lemtalsi, Tahira
Eldahshan, Wael
Xu, Zhimin
Saul, Alan
Elmasry, Khaled
Al-Shabrawey, Mohamed
Caldwell, Ruth B.
Caldwell, R. William
author_facet Atawia, Reem T.
Bunch, Katharine L.
Fouda, Abdelrahman Y.
Lemtalsi, Tahira
Eldahshan, Wael
Xu, Zhimin
Saul, Alan
Elmasry, Khaled
Al-Shabrawey, Mohamed
Caldwell, Ruth B.
Caldwell, R. William
author_sort Atawia, Reem T.
collection PubMed
description Western diet-induced obesity is linked to the development of metabolic dysfunctions, including type 2 diabetes and complications that include retinopathy, a leading cause of blindness. Aberrant activation of the inflammasome cascade leads to the progression of obesity-induced pathologies. Our lab showed the critical role of arginase 2 (A2), the mitochondrial isoform of this ureahydrolase, in obesity-induced metabolic dysfunction and inflammation. A2 deletion also has been shown to be protective against retinal inflammation in models of ischemic retinopathy and multiple sclerosis. We investigated the effect of A2 deletion on western diet-induced retinopathy. Wild-type mice fed a high-fat, high-sucrose western diet for 16 weeks exhibited elevated retinal expression of A2, markers of the inflammasome pathway, oxidative stress, and activation of microglia/macrophages. Western diet feeding induced exaggerated retinal light responses without affecting visual acuity or retinal morphology. These effects were reduced or absent in mice with global A2 deletion. Exposure of retinal endothelial cells to palmitate and high glucose, a mimic of the obese state, increased expression of A2 and inflammatory mediators and induced cell death. These effects, except for A2, were prevented by pretreatment with an arginase inhibitor. Collectively, our study demonstrated a substantial role of A2 in early manifestations of diabetic retinopathy.
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spelling pubmed-70739402020-03-19 Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity Atawia, Reem T. Bunch, Katharine L. Fouda, Abdelrahman Y. Lemtalsi, Tahira Eldahshan, Wael Xu, Zhimin Saul, Alan Elmasry, Khaled Al-Shabrawey, Mohamed Caldwell, Ruth B. Caldwell, R. William J Clin Med Article Western diet-induced obesity is linked to the development of metabolic dysfunctions, including type 2 diabetes and complications that include retinopathy, a leading cause of blindness. Aberrant activation of the inflammasome cascade leads to the progression of obesity-induced pathologies. Our lab showed the critical role of arginase 2 (A2), the mitochondrial isoform of this ureahydrolase, in obesity-induced metabolic dysfunction and inflammation. A2 deletion also has been shown to be protective against retinal inflammation in models of ischemic retinopathy and multiple sclerosis. We investigated the effect of A2 deletion on western diet-induced retinopathy. Wild-type mice fed a high-fat, high-sucrose western diet for 16 weeks exhibited elevated retinal expression of A2, markers of the inflammasome pathway, oxidative stress, and activation of microglia/macrophages. Western diet feeding induced exaggerated retinal light responses without affecting visual acuity or retinal morphology. These effects were reduced or absent in mice with global A2 deletion. Exposure of retinal endothelial cells to palmitate and high glucose, a mimic of the obese state, increased expression of A2 and inflammatory mediators and induced cell death. These effects, except for A2, were prevented by pretreatment with an arginase inhibitor. Collectively, our study demonstrated a substantial role of A2 in early manifestations of diabetic retinopathy. MDPI 2020-01-22 /pmc/articles/PMC7073940/ /pubmed/31979105 http://dx.doi.org/10.3390/jcm9020317 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Atawia, Reem T.
Bunch, Katharine L.
Fouda, Abdelrahman Y.
Lemtalsi, Tahira
Eldahshan, Wael
Xu, Zhimin
Saul, Alan
Elmasry, Khaled
Al-Shabrawey, Mohamed
Caldwell, Ruth B.
Caldwell, R. William
Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity
title Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity
title_full Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity
title_fullStr Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity
title_full_unstemmed Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity
title_short Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity
title_sort role of arginase 2 in murine retinopathy associated with western diet-induced obesity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073940/
https://www.ncbi.nlm.nih.gov/pubmed/31979105
http://dx.doi.org/10.3390/jcm9020317
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