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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creator | 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 |
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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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.</description><identifier>ISSN: 2077-0383</identifier><identifier>EISSN: 2077-0383</identifier><identifier>DOI: 10.3390/jcm9020317</identifier><identifier>PMID: 31979105</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Antibodies ; Clinical medicine ; Cytokines ; Diabetes ; Diabetic retinopathy ; Diet ; Glucose ; Inflammation ; Laboratories ; Metabolism ; Nitric oxide ; Obesity ; Oxidative stress ; Proteins ; Retina ; Sucrose</subject><ispartof>Journal of clinical medicine, 2020-01, Vol.9 (2), p.317</ispartof><rights>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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-84611a1febd74f0b87191df9d3baa00896383b5a7d35a4340b4eddacb6df0c743</citedby><cites>FETCH-LOGICAL-c406t-84611a1febd74f0b87191df9d3baa00896383b5a7d35a4340b4eddacb6df0c743</cites><orcidid>0000-0001-5277-441X ; 0000-0003-2184-1629</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073940/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073940/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31979105$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Atawia, Reem T</creatorcontrib><creatorcontrib>Bunch, Katharine L</creatorcontrib><creatorcontrib>Fouda, Abdelrahman Y</creatorcontrib><creatorcontrib>Lemtalsi, Tahira</creatorcontrib><creatorcontrib>Eldahshan, Wael</creatorcontrib><creatorcontrib>Xu, Zhimin</creatorcontrib><creatorcontrib>Saul, Alan</creatorcontrib><creatorcontrib>Elmasry, Khaled</creatorcontrib><creatorcontrib>Al-Shabrawey, Mohamed</creatorcontrib><creatorcontrib>Caldwell, Ruth B</creatorcontrib><creatorcontrib>Caldwell, R William</creatorcontrib><title>Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity</title><title>Journal of clinical medicine</title><addtitle>J Clin Med</addtitle><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. 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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.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Clinical medicine</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Diabetic retinopathy</subject><subject>Diet</subject><subject>Glucose</subject><subject>Inflammation</subject><subject>Laboratories</subject><subject>Metabolism</subject><subject>Nitric oxide</subject><subject>Obesity</subject><subject>Oxidative stress</subject><subject>Proteins</subject><subject>Retina</subject><subject>Sucrose</subject><issn>2077-0383</issn><issn>2077-0383</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpVUU1LAzEQDaLYUnvxB0jAm7CabLKb3YtQ6lehUigWjyG7ybYpbVKTrNJ_b6S11rnMwDzevHkPgEuMbgkp0d2yXpcoRQSzE9BNEWMJIgU5PZo7oO_9EsUqCppidg46BJesxCjrgtnUrhS0DRy4uTbCK5hCbeBr67RRcKqCNnYjwmILB97bWougJPzSYQHflQ_KGfigVUhGRrZ13Ewq5XXYXoCzRqy86u97D8yeHt-GL8l48jwaDsZJTVEekoLmGAvcqEoy2qCqYLjEsiklqYSIcss8yq8ywSTJBCUUVVRJKeoqlw2qGSU9cL_j3bTVWslameDEim-cXgu35VZo_n9j9ILP7SdniJGSokhwvSdw9qONH_GlbZ2Jmnma0-gQziiOqJsdqnbWe6eawwWM-E8K_C-FCL461nSA_npOvgEWMIMA</recordid><startdate>20200122</startdate><enddate>20200122</enddate><creator>Atawia, Reem T</creator><creator>Bunch, Katharine L</creator><creator>Fouda, Abdelrahman Y</creator><creator>Lemtalsi, Tahira</creator><creator>Eldahshan, Wael</creator><creator>Xu, Zhimin</creator><creator>Saul, Alan</creator><creator>Elmasry, Khaled</creator><creator>Al-Shabrawey, Mohamed</creator><creator>Caldwell, Ruth B</creator><creator>Caldwell, R William</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5277-441X</orcidid><orcidid>https://orcid.org/0000-0003-2184-1629</orcidid></search><sort><creationdate>20200122</creationdate><title>Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-84611a1febd74f0b87191df9d3baa00896383b5a7d35a4340b4eddacb6df0c743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Clinical medicine</topic><topic>Cytokines</topic><topic>Diabetes</topic><topic>Diabetic retinopathy</topic><topic>Diet</topic><topic>Glucose</topic><topic>Inflammation</topic><topic>Laboratories</topic><topic>Metabolism</topic><topic>Nitric oxide</topic><topic>Obesity</topic><topic>Oxidative stress</topic><topic>Proteins</topic><topic>Retina</topic><topic>Sucrose</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Atawia, Reem T</creatorcontrib><creatorcontrib>Bunch, Katharine L</creatorcontrib><creatorcontrib>Fouda, Abdelrahman Y</creatorcontrib><creatorcontrib>Lemtalsi, Tahira</creatorcontrib><creatorcontrib>Eldahshan, Wael</creatorcontrib><creatorcontrib>Xu, Zhimin</creatorcontrib><creatorcontrib>Saul, Alan</creatorcontrib><creatorcontrib>Elmasry, Khaled</creatorcontrib><creatorcontrib>Al-Shabrawey, Mohamed</creatorcontrib><creatorcontrib>Caldwell, Ruth B</creatorcontrib><creatorcontrib>Caldwell, R William</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Atawia, Reem T</au><au>Bunch, Katharine L</au><au>Fouda, Abdelrahman Y</au><au>Lemtalsi, Tahira</au><au>Eldahshan, Wael</au><au>Xu, Zhimin</au><au>Saul, Alan</au><au>Elmasry, Khaled</au><au>Al-Shabrawey, Mohamed</au><au>Caldwell, Ruth B</au><au>Caldwell, R William</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity</atitle><jtitle>Journal of clinical medicine</jtitle><addtitle>J Clin Med</addtitle><date>2020-01-22</date><risdate>2020</risdate><volume>9</volume><issue>2</issue><spage>317</spage><pages>317-</pages><issn>2077-0383</issn><eissn>2077-0383</eissn><abstract>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. 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subjects | Animals Antibodies Clinical medicine Cytokines Diabetes Diabetic retinopathy Diet Glucose Inflammation Laboratories Metabolism Nitric oxide Obesity Oxidative stress Proteins Retina Sucrose |
title | Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity |
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