Adipocyte Hypoxia Increases Hepatocyte Hepcidin Expression
Hepcidin plays a key role in regulating iron metabolism by blocking iron efflux from macrophages and enterocytes. Hepcidin is synthesized primarily in the liver, and its expression is increased by iron overload and inflammation. Obesity is associated with chronic inflammation as well as poor iron st...
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| Veröffentlicht in: | Biological trace element research 2011-11, Vol.143 (2), p.764-771 |
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| creator | Hintze, Korry Joseph Snow, Dallin Nabor, Darren Timbimboo, Hunter |
| description | Hepcidin plays a key role in regulating iron metabolism by blocking iron efflux from macrophages and enterocytes. Hepcidin is synthesized primarily in the liver, and its expression is increased by iron overload and inflammation. Obesity is associated with chronic inflammation as well as poor iron status. Central obesity causes adipocyte hypoxia resulting in chronic inflammation. Therefore, the objective of the present study was to determine if adipocyte hypoxia and associated inflammation signal hepatocyte hepcidin expression. The effect of adipocyte hypoxia on hepcidin expression was modeled using a 3T3-L1 adipocyte/Huh7 hepatocyte co-culture model. Adipocytes were cultured at either standard conditions (19% O
2
) or hypoxic conditions (1% O
2
). Compared to standard conditions, hypoxic 3T3-L1 cells had significantly higher IL-6 and leptin expression. Treatment of Huh7 cells with media from hypoxic or LPS-treated 3T3-L1 adipocytes significantly increased hepcidin promoter activity and mRNA compared to cells treated with normoxic 3T3-L1 media or control media. When the hepcidin STAT3 binding site was mutated, promoter activation by hypoxic media was abrogated. These data suggest that adipocyte hypoxia (a feature of central obesity) may increase hepcidin expression and plays a role in the association between obesity and poor iron status. |
| doi_str_mv | 10.1007/s12011-010-8932-6 |
| format | Article |
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2
) or hypoxic conditions (1% O
2
). Compared to standard conditions, hypoxic 3T3-L1 cells had significantly higher IL-6 and leptin expression. Treatment of Huh7 cells with media from hypoxic or LPS-treated 3T3-L1 adipocytes significantly increased hepcidin promoter activity and mRNA compared to cells treated with normoxic 3T3-L1 media or control media. When the hepcidin STAT3 binding site was mutated, promoter activation by hypoxic media was abrogated. These data suggest that adipocyte hypoxia (a feature of central obesity) may increase hepcidin expression and plays a role in the association between obesity and poor iron status.</description><identifier>ISSN: 0163-4984</identifier><identifier>EISSN: 1559-0720</identifier><identifier>DOI: 10.1007/s12011-010-8932-6</identifier><identifier>PMID: 21181293</identifier><language>eng</language><publisher>New York: Humana Press Inc</publisher><subject>3T3-L1 Cells ; adipocytes ; Adipocytes - drug effects ; Adipocytes - metabolism ; Animals ; Antimicrobial Cationic Peptides - genetics ; Antimicrobial Cationic Peptides - metabolism ; Biochemistry ; Biomedical and Life Sciences ; Biotechnology ; Cell Hypoxia - physiology ; Cell Line ; coculture ; Culture Media, Conditioned - pharmacology ; enterocytes ; Gene expression ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; hepcidin ; Hepcidins ; Humans ; Hypoxia ; inflammation ; interleukin-6 ; Iron ; iron absorption ; iron overload ; leptin ; Life Sciences ; Lipopolysaccharides - pharmacology ; liver ; macrophages ; Mice ; Nutrition ; Obesity ; Oncology ; Polymerase Chain Reaction ; Promoter Regions, Genetic - drug effects ; Promoter Regions, Genetic - genetics</subject><ispartof>Biological trace element research, 2011-11, Vol.143 (2), p.764-771</ispartof><rights>Springer Science+Business Media, LLC 2010</rights><rights>Springer Science+Business Media, LLC 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c403t-3942e74b6be540933f3234e56a8b96ed5dabf5b0fb97742bb1d311cc3a8a414b3</citedby><cites>FETCH-LOGICAL-c403t-3942e74b6be540933f3234e56a8b96ed5dabf5b0fb97742bb1d311cc3a8a414b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12011-010-8932-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12011-010-8932-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27915,27916,41479,42548,51310</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21181293$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hintze, Korry Joseph</creatorcontrib><creatorcontrib>Snow, Dallin</creatorcontrib><creatorcontrib>Nabor, Darren</creatorcontrib><creatorcontrib>Timbimboo, Hunter</creatorcontrib><title>Adipocyte Hypoxia Increases Hepatocyte Hepcidin Expression</title><title>Biological trace element research</title><addtitle>Biol Trace Elem Res</addtitle><addtitle>Biol Trace Elem Res</addtitle><description>Hepcidin plays a key role in regulating iron metabolism by blocking iron efflux from macrophages and enterocytes. Hepcidin is synthesized primarily in the liver, and its expression is increased by iron overload and inflammation. Obesity is associated with chronic inflammation as well as poor iron status. Central obesity causes adipocyte hypoxia resulting in chronic inflammation. Therefore, the objective of the present study was to determine if adipocyte hypoxia and associated inflammation signal hepatocyte hepcidin expression. The effect of adipocyte hypoxia on hepcidin expression was modeled using a 3T3-L1 adipocyte/Huh7 hepatocyte co-culture model. Adipocytes were cultured at either standard conditions (19% O
2
) or hypoxic conditions (1% O
2
). Compared to standard conditions, hypoxic 3T3-L1 cells had significantly higher IL-6 and leptin expression. Treatment of Huh7 cells with media from hypoxic or LPS-treated 3T3-L1 adipocytes significantly increased hepcidin promoter activity and mRNA compared to cells treated with normoxic 3T3-L1 media or control media. When the hepcidin STAT3 binding site was mutated, promoter activation by hypoxic media was abrogated. These data suggest that adipocyte hypoxia (a feature of central obesity) may increase hepcidin expression and plays a role in the association between obesity and poor iron status.</description><subject>3T3-L1 Cells</subject><subject>adipocytes</subject><subject>Adipocytes - drug effects</subject><subject>Adipocytes - metabolism</subject><subject>Animals</subject><subject>Antimicrobial Cationic Peptides - genetics</subject><subject>Antimicrobial Cationic Peptides - metabolism</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biotechnology</subject><subject>Cell Hypoxia - physiology</subject><subject>Cell Line</subject><subject>coculture</subject><subject>Culture Media, Conditioned - pharmacology</subject><subject>enterocytes</subject><subject>Gene expression</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>hepcidin</subject><subject>Hepcidins</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>inflammation</subject><subject>interleukin-6</subject><subject>Iron</subject><subject>iron absorption</subject><subject>iron overload</subject><subject>leptin</subject><subject>Life Sciences</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>liver</subject><subject>macrophages</subject><subject>Mice</subject><subject>Nutrition</subject><subject>Obesity</subject><subject>Oncology</subject><subject>Polymerase Chain Reaction</subject><subject>Promoter Regions, Genetic - drug effects</subject><subject>Promoter Regions, Genetic - genetics</subject><issn>0163-4984</issn><issn>1559-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU1LAzEQhoMotlZ_gBcpXvSymkmy2cRbKdUWCl70HJLdWdnS7q5JF-y_N2WrgqCnGZhn3vl4CbkEegeUZvcBGAVIKNBEac4SeUSGkKY6oRmjx2RIQfJEaCUG5CyEFaWQMc1PyYABKIjpkDxMiqpt8t0Wx_Nd23xUdryoc482YBjPsbXbQxHbvCqqejz7aD2GUDX1OTkp7TrgxSGOyOvj7GU6T5bPT4vpZJnkgvJtwrVgmAknHaaCas5LzrjAVFrltMQiLawrU0dLp7NMMOeg4AB5zq2yAoTjI3LT67a-ee8wbM2mCjmu17bGpgtGaamYglRG8vZfkkPKJQURnzUi17_QVdP5Ot6x14uLS6kiBD2U-yYEj6VpfbWxfmeAmr0DpnfARAfM3gGz3-HqINy5DRbfHV8vjwDrgRBL9Rv6n8l_q34C3uyPDw</recordid><startdate>20111101</startdate><enddate>20111101</enddate><creator>Hintze, Korry Joseph</creator><creator>Snow, Dallin</creator><creator>Nabor, Darren</creator><creator>Timbimboo, Hunter</creator><general>Humana Press Inc</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QH</scope><scope>7QP</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H97</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L.G</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7S9</scope><scope>L.6</scope><scope>7X8</scope></search><sort><creationdate>20111101</creationdate><title>Adipocyte Hypoxia Increases Hepatocyte Hepcidin Expression</title><author>Hintze, Korry Joseph ; Snow, Dallin ; Nabor, Darren ; Timbimboo, Hunter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c403t-3942e74b6be540933f3234e56a8b96ed5dabf5b0fb97742bb1d311cc3a8a414b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>3T3-L1 Cells</topic><topic>adipocytes</topic><topic>Adipocytes - drug effects</topic><topic>Adipocytes - metabolism</topic><topic>Animals</topic><topic>Antimicrobial Cationic Peptides - genetics</topic><topic>Antimicrobial Cationic Peptides - metabolism</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biotechnology</topic><topic>Cell Hypoxia - physiology</topic><topic>Cell Line</topic><topic>coculture</topic><topic>Culture Media, Conditioned - pharmacology</topic><topic>enterocytes</topic><topic>Gene expression</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - metabolism</topic><topic>hepcidin</topic><topic>Hepcidins</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>inflammation</topic><topic>interleukin-6</topic><topic>Iron</topic><topic>iron absorption</topic><topic>iron overload</topic><topic>leptin</topic><topic>Life Sciences</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>liver</topic><topic>macrophages</topic><topic>Mice</topic><topic>Nutrition</topic><topic>Obesity</topic><topic>Oncology</topic><topic>Polymerase Chain Reaction</topic><topic>Promoter Regions, Genetic - drug effects</topic><topic>Promoter Regions, Genetic - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hintze, Korry Joseph</creatorcontrib><creatorcontrib>Snow, Dallin</creatorcontrib><creatorcontrib>Nabor, Darren</creatorcontrib><creatorcontrib>Timbimboo, Hunter</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Aqualine</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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 One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</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 Basic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>MEDLINE - Academic</collection><jtitle>Biological trace element research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hintze, Korry Joseph</au><au>Snow, Dallin</au><au>Nabor, Darren</au><au>Timbimboo, Hunter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipocyte Hypoxia Increases Hepatocyte Hepcidin Expression</atitle><jtitle>Biological trace element research</jtitle><stitle>Biol Trace Elem Res</stitle><addtitle>Biol Trace Elem Res</addtitle><date>2011-11-01</date><risdate>2011</risdate><volume>143</volume><issue>2</issue><spage>764</spage><epage>771</epage><pages>764-771</pages><issn>0163-4984</issn><eissn>1559-0720</eissn><abstract>Hepcidin plays a key role in regulating iron metabolism by blocking iron efflux from macrophages and enterocytes. Hepcidin is synthesized primarily in the liver, and its expression is increased by iron overload and inflammation. Obesity is associated with chronic inflammation as well as poor iron status. Central obesity causes adipocyte hypoxia resulting in chronic inflammation. Therefore, the objective of the present study was to determine if adipocyte hypoxia and associated inflammation signal hepatocyte hepcidin expression. The effect of adipocyte hypoxia on hepcidin expression was modeled using a 3T3-L1 adipocyte/Huh7 hepatocyte co-culture model. Adipocytes were cultured at either standard conditions (19% O
2
) or hypoxic conditions (1% O
2
). Compared to standard conditions, hypoxic 3T3-L1 cells had significantly higher IL-6 and leptin expression. Treatment of Huh7 cells with media from hypoxic or LPS-treated 3T3-L1 adipocytes significantly increased hepcidin promoter activity and mRNA compared to cells treated with normoxic 3T3-L1 media or control media. When the hepcidin STAT3 binding site was mutated, promoter activation by hypoxic media was abrogated. These data suggest that adipocyte hypoxia (a feature of central obesity) may increase hepcidin expression and plays a role in the association between obesity and poor iron status.</abstract><cop>New York</cop><pub>Humana Press Inc</pub><pmid>21181293</pmid><doi>10.1007/s12011-010-8932-6</doi><tpages>8</tpages></addata></record> |
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| subjects | 3T3-L1 Cells adipocytes Adipocytes - drug effects Adipocytes - metabolism Animals Antimicrobial Cationic Peptides - genetics Antimicrobial Cationic Peptides - metabolism Biochemistry Biomedical and Life Sciences Biotechnology Cell Hypoxia - physiology Cell Line coculture Culture Media, Conditioned - pharmacology enterocytes Gene expression Hepatocytes - drug effects Hepatocytes - metabolism hepcidin Hepcidins Humans Hypoxia inflammation interleukin-6 Iron iron absorption iron overload leptin Life Sciences Lipopolysaccharides - pharmacology liver macrophages Mice Nutrition Obesity Oncology Polymerase Chain Reaction Promoter Regions, Genetic - drug effects Promoter Regions, Genetic - genetics |
| title | Adipocyte Hypoxia Increases Hepatocyte Hepcidin Expression |
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