Arginine and glutamine availability and macrophage functions in the obese insulin-resistant Zucker Rat

Increased susceptibility to infections in obese patients may be related to decreased availability of arginine and glutamine, which may affect immune cell functions. Our aim was to evaluate the in vitro effects of these amino acids on the function of macrophages from obese insulin‐resistant Zucker ra...

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Veröffentlicht in:Journal of cellular physiology 2005-01, Vol.202 (1), p.153-159
Hauptverfasser: Blanc, Marie-Céline, Moinard, Christophe, Béziel, Aurélie, Darquy, Sylviane, Cynober, Luc, De Bandt, Jean-Pascal
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container_title Journal of cellular physiology
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creator Blanc, Marie-Céline
Moinard, Christophe
Béziel, Aurélie
Darquy, Sylviane
Cynober, Luc
De Bandt, Jean-Pascal
description Increased susceptibility to infections in obese patients may be related to decreased availability of arginine and glutamine, which may affect immune cell functions. Our aim was to evaluate the in vitro effects of these amino acids on the function of macrophages from obese insulin‐resistant Zucker rats. Macrophages, isolated from male Zucker obese or lean rats by peritoneal lavage, were incubated in Dulbecco's modified Eagle medium (DMEM) without arginine or glutamine. Arginine or glutamine was added to the medium at increasing final concentrations (0, 0.25, 0.5, 1 or 2 mM). After stimulation by lipopolysaccharide (LPS) from E. coli (40 μg/ml), productions of tumour necrosis factor α (TNFα) and of nitric oxide (NO) were measured after 3 or 48 h incubation, respectively. NO production, lower in macrophages from obese rats, decreased in macrophages from lean rats (0 mM: 2,423 ± 1,174 vs. 2 mM: 198 ± 31 μM/mg protein/24 h; P 
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Our aim was to evaluate the in vitro effects of these amino acids on the function of macrophages from obese insulin‐resistant Zucker rats. Macrophages, isolated from male Zucker obese or lean rats by peritoneal lavage, were incubated in Dulbecco's modified Eagle medium (DMEM) without arginine or glutamine. Arginine or glutamine was added to the medium at increasing final concentrations (0, 0.25, 0.5, 1 or 2 mM). After stimulation by lipopolysaccharide (LPS) from E. coli (40 μg/ml), productions of tumour necrosis factor α (TNFα) and of nitric oxide (NO) were measured after 3 or 48 h incubation, respectively. NO production, lower in macrophages from obese rats, decreased in macrophages from lean rats (0 mM: 2,423 ± 1,174 vs. 2 mM: 198 ± 31 μM/mg protein/24 h; P &lt; 0.05), but not in those from obese rats, when glutamine was added. TNFα production, lower in macrophages from obese rats, was inversely correlated with glutamine concentration. In the presence of arginine, NO production was constantly higher in macrophages from obese rats. It peaked at 0.5 mM arginine and decreased thereafter in both groups. TNFα production in macrophages from lean rats was unaffected by arginine, but decreased in macrophages from obese rats (0 mM: 1920 ± 450 vs. 2 mM: 810 ± 90 μM/mg protein/3 h; P &lt; 0.05). These results suggest that abnormalities in cell signalling or in arginine and glutamine metabolism in macrophages of obese rats, resulting in decreased TNFα production and increased NO release, may contribute to increased susceptibility to infection in insulin‐resistant states. © 2005 Wiley‐Liss, Inc.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.20092</identifier><identifier>PMID: 15389544</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Arginine - metabolism ; Arginine - pharmacology ; Cells, Cultured ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Down-Regulation - drug effects ; Down-Regulation - genetics ; Down-Regulation - immunology ; Genetic Predisposition to Disease - genetics ; Glutamine - metabolism ; Glutamine - pharmacology ; Immune System - drug effects ; Immune System - immunology ; Immunity, Innate - drug effects ; Immunity, Innate - genetics ; Infection - genetics ; Infection - immunology ; Insulin Resistance - genetics ; Insulin Resistance - physiology ; Lipopolysaccharides ; Macrophages - drug effects ; Macrophages - metabolism ; Male ; Nitric Oxide - metabolism ; Obesity - complications ; Obesity - genetics ; Obesity - immunology ; Rats ; Rats, Zucker ; Signal Transduction - drug effects ; Signal Transduction - genetics ; Signal Transduction - immunology ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Journal of cellular physiology, 2005-01, Vol.202 (1), p.153-159</ispartof><rights>Copyright © 2005 Wiley‐Liss, Inc.</rights><rights>2005 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3612-3a7736f2a40c77040a6fd61577995f821b9d57579278491718d2aa8b1ec0b3dc3</citedby><cites>FETCH-LOGICAL-c3612-3a7736f2a40c77040a6fd61577995f821b9d57579278491718d2aa8b1ec0b3dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.20092$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.20092$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15389544$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Blanc, Marie-Céline</creatorcontrib><creatorcontrib>Moinard, Christophe</creatorcontrib><creatorcontrib>Béziel, Aurélie</creatorcontrib><creatorcontrib>Darquy, Sylviane</creatorcontrib><creatorcontrib>Cynober, Luc</creatorcontrib><creatorcontrib>De Bandt, Jean-Pascal</creatorcontrib><title>Arginine and glutamine availability and macrophage functions in the obese insulin-resistant Zucker Rat</title><title>Journal of cellular physiology</title><addtitle>J. Cell. Physiol</addtitle><description>Increased susceptibility to infections in obese patients may be related to decreased availability of arginine and glutamine, which may affect immune cell functions. Our aim was to evaluate the in vitro effects of these amino acids on the function of macrophages from obese insulin‐resistant Zucker rats. Macrophages, isolated from male Zucker obese or lean rats by peritoneal lavage, were incubated in Dulbecco's modified Eagle medium (DMEM) without arginine or glutamine. Arginine or glutamine was added to the medium at increasing final concentrations (0, 0.25, 0.5, 1 or 2 mM). After stimulation by lipopolysaccharide (LPS) from E. coli (40 μg/ml), productions of tumour necrosis factor α (TNFα) and of nitric oxide (NO) were measured after 3 or 48 h incubation, respectively. NO production, lower in macrophages from obese rats, decreased in macrophages from lean rats (0 mM: 2,423 ± 1,174 vs. 2 mM: 198 ± 31 μM/mg protein/24 h; P &lt; 0.05), but not in those from obese rats, when glutamine was added. TNFα production, lower in macrophages from obese rats, was inversely correlated with glutamine concentration. In the presence of arginine, NO production was constantly higher in macrophages from obese rats. It peaked at 0.5 mM arginine and decreased thereafter in both groups. TNFα production in macrophages from lean rats was unaffected by arginine, but decreased in macrophages from obese rats (0 mM: 1920 ± 450 vs. 2 mM: 810 ± 90 μM/mg protein/3 h; P &lt; 0.05). 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Cell. Physiol</addtitle><date>2005-01</date><risdate>2005</risdate><volume>202</volume><issue>1</issue><spage>153</spage><epage>159</epage><pages>153-159</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>Increased susceptibility to infections in obese patients may be related to decreased availability of arginine and glutamine, which may affect immune cell functions. Our aim was to evaluate the in vitro effects of these amino acids on the function of macrophages from obese insulin‐resistant Zucker rats. Macrophages, isolated from male Zucker obese or lean rats by peritoneal lavage, were incubated in Dulbecco's modified Eagle medium (DMEM) without arginine or glutamine. Arginine or glutamine was added to the medium at increasing final concentrations (0, 0.25, 0.5, 1 or 2 mM). After stimulation by lipopolysaccharide (LPS) from E. coli (40 μg/ml), productions of tumour necrosis factor α (TNFα) and of nitric oxide (NO) were measured after 3 or 48 h incubation, respectively. NO production, lower in macrophages from obese rats, decreased in macrophages from lean rats (0 mM: 2,423 ± 1,174 vs. 2 mM: 198 ± 31 μM/mg protein/24 h; P &lt; 0.05), but not in those from obese rats, when glutamine was added. TNFα production, lower in macrophages from obese rats, was inversely correlated with glutamine concentration. In the presence of arginine, NO production was constantly higher in macrophages from obese rats. It peaked at 0.5 mM arginine and decreased thereafter in both groups. TNFα production in macrophages from lean rats was unaffected by arginine, but decreased in macrophages from obese rats (0 mM: 1920 ± 450 vs. 2 mM: 810 ± 90 μM/mg protein/3 h; P &lt; 0.05). These results suggest that abnormalities in cell signalling or in arginine and glutamine metabolism in macrophages of obese rats, resulting in decreased TNFα production and increased NO release, may contribute to increased susceptibility to infection in insulin‐resistant states. © 2005 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15389544</pmid><doi>10.1002/jcp.20092</doi><tpages>7</tpages></addata></record>
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subjects Animals
Arginine - metabolism
Arginine - pharmacology
Cells, Cultured
Disease Models, Animal
Dose-Response Relationship, Drug
Down-Regulation - drug effects
Down-Regulation - genetics
Down-Regulation - immunology
Genetic Predisposition to Disease - genetics
Glutamine - metabolism
Glutamine - pharmacology
Immune System - drug effects
Immune System - immunology
Immunity, Innate - drug effects
Immunity, Innate - genetics
Infection - genetics
Infection - immunology
Insulin Resistance - genetics
Insulin Resistance - physiology
Lipopolysaccharides
Macrophages - drug effects
Macrophages - metabolism
Male
Nitric Oxide - metabolism
Obesity - complications
Obesity - genetics
Obesity - immunology
Rats
Rats, Zucker
Signal Transduction - drug effects
Signal Transduction - genetics
Signal Transduction - immunology
Tumor Necrosis Factor-alpha - metabolism
title Arginine and glutamine availability and macrophage functions in the obese insulin-resistant Zucker Rat
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