Omentin‐regulated proteins combine a pro‐inflammatory phenotype with an anti‐inflammatory counterregulation in human adipocytes: A proteomics analysis

Aims Experimental and epidemiological studies reported controversial data on the role of omentin in type 2 diabetes and cardiovascular diseases. This study aimed to characterise the impact of omentin on the secretome of human adipocytes to analyse the enrichment of these proteins in metabolic and ce...

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Veröffentlicht in:Diabetes/metabolism research and reviews 2019-01, Vol.35 (1), p.e3074-n/a
Hauptverfasser: Niersmann, Corinna, Hauck, Stefanie M., Kannenberg, Julia M., Röhrig, Karin, Toerne, Christine, Roden, Michael, Herder, Christian, Carstensen‐Kirberg, Maren
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container_issue 1
container_start_page e3074
container_title Diabetes/metabolism research and reviews
container_volume 35
creator Niersmann, Corinna
Hauck, Stefanie M.
Kannenberg, Julia M.
Röhrig, Karin
Toerne, Christine
Roden, Michael
Herder, Christian
Carstensen‐Kirberg, Maren
description Aims Experimental and epidemiological studies reported controversial data on the role of omentin in type 2 diabetes and cardiovascular diseases. This study aimed to characterise the impact of omentin on the secretome of human adipocytes to analyse the enrichment of these proteins in metabolic and cellular signalling pathways underlying its physiological function. Material/methods Differentiated primary human adipocytes were treated without or with 500 or 2000 ng/mL omentin for 24 hours. The secretome was analysed by liquid chromatography coupled tandem‐mass spectrometry. Differences in protein secretion between untreated and omentin‐treated adipocytes were compared using a paired t‐test. Other potential upstream regulators and the overrepresentation in canonical pathways of omentin‐stimulated proteins were analysed using Ingenuity Pathway Analysis. Results The supernatant of adipocytes contained 3493 proteins, of which 140 were differentially secreted by both concentrations of omentin compared with untreated adipocytes. Among the most strongly increased proteins, tumour necrosis factor‐inducible gene 6 protein (TNFAIP6) was increased by 140‐fold in the supernatant. Omentin‐regulated proteins were overrepresented in seven canonical pathways including eukaryotic initiation factor 2 signalling, complement system, and inhibition of matrix metalloproteases. We further identified 25 other potential upstream activators of omentin‐regulated proteins, mainly pro‐inflammatory cytokines and transcription regulators including NFκB. Conclusions In differentiated human adipocytes, the release of the anti‐inflammatory TNFAIP6 might be part of a counterregulatory response to the pro‐inflammatory action of omentin. Omentin‐regulated proteins were overrepresented in pathways indicating cellular stress, a pro‐inflammatory environment and a crosstalk with other organs. Other potential activators of omentin‐regulated proteins point towards a central role of NFκB activation in the omentin‐induced secretory process.
doi_str_mv 10.1002/dmrr.3074
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This study aimed to characterise the impact of omentin on the secretome of human adipocytes to analyse the enrichment of these proteins in metabolic and cellular signalling pathways underlying its physiological function. Material/methods Differentiated primary human adipocytes were treated without or with 500 or 2000 ng/mL omentin for 24 hours. The secretome was analysed by liquid chromatography coupled tandem‐mass spectrometry. Differences in protein secretion between untreated and omentin‐treated adipocytes were compared using a paired t‐test. Other potential upstream regulators and the overrepresentation in canonical pathways of omentin‐stimulated proteins were analysed using Ingenuity Pathway Analysis. Results The supernatant of adipocytes contained 3493 proteins, of which 140 were differentially secreted by both concentrations of omentin compared with untreated adipocytes. Among the most strongly increased proteins, tumour necrosis factor‐inducible gene 6 protein (TNFAIP6) was increased by 140‐fold in the supernatant. Omentin‐regulated proteins were overrepresented in seven canonical pathways including eukaryotic initiation factor 2 signalling, complement system, and inhibition of matrix metalloproteases. We further identified 25 other potential upstream activators of omentin‐regulated proteins, mainly pro‐inflammatory cytokines and transcription regulators including NFκB. Conclusions In differentiated human adipocytes, the release of the anti‐inflammatory TNFAIP6 might be part of a counterregulatory response to the pro‐inflammatory action of omentin. Omentin‐regulated proteins were overrepresented in pathways indicating cellular stress, a pro‐inflammatory environment and a crosstalk with other organs. Other potential activators of omentin‐regulated proteins point towards a central role of NFκB activation in the omentin‐induced secretory process.</description><identifier>ISSN: 1520-7552</identifier><identifier>EISSN: 1520-7560</identifier><identifier>DOI: 10.1002/dmrr.3074</identifier><identifier>PMID: 30198166</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adipocytes ; Cardiovascular diseases ; Cellular stress response ; Complement activation ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Inflammation ; Liquid chromatography ; Mass spectroscopy ; NF-κB protein ; Obesity ; omentin ; Phenotypes ; Protein folding ; Proteins ; Proteomics ; Secretome ; Signal transduction ; Transcription ; Tumor necrosis factor ; Tumors</subject><ispartof>Diabetes/metabolism research and reviews, 2019-01, Vol.35 (1), p.e3074-n/a</ispartof><rights>2018 John Wiley &amp; Sons, Ltd.</rights><rights>2019 John Wiley &amp; Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3884-c264a3936b94df0485d5ea62bcd64d6f4dc922c09afcd1c84756ba499348728d3</citedby><cites>FETCH-LOGICAL-c3884-c264a3936b94df0485d5ea62bcd64d6f4dc922c09afcd1c84756ba499348728d3</cites><orcidid>0000-0002-2050-093X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fdmrr.3074$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fdmrr.3074$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,27931,27932,45581,45582</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30198166$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Niersmann, Corinna</creatorcontrib><creatorcontrib>Hauck, Stefanie M.</creatorcontrib><creatorcontrib>Kannenberg, Julia M.</creatorcontrib><creatorcontrib>Röhrig, Karin</creatorcontrib><creatorcontrib>Toerne, Christine</creatorcontrib><creatorcontrib>Roden, Michael</creatorcontrib><creatorcontrib>Herder, Christian</creatorcontrib><creatorcontrib>Carstensen‐Kirberg, Maren</creatorcontrib><title>Omentin‐regulated proteins combine a pro‐inflammatory phenotype with an anti‐inflammatory counterregulation in human adipocytes: A proteomics analysis</title><title>Diabetes/metabolism research and reviews</title><addtitle>Diabetes Metab Res Rev</addtitle><description>Aims Experimental and epidemiological studies reported controversial data on the role of omentin in type 2 diabetes and cardiovascular diseases. This study aimed to characterise the impact of omentin on the secretome of human adipocytes to analyse the enrichment of these proteins in metabolic and cellular signalling pathways underlying its physiological function. Material/methods Differentiated primary human adipocytes were treated without or with 500 or 2000 ng/mL omentin for 24 hours. The secretome was analysed by liquid chromatography coupled tandem‐mass spectrometry. Differences in protein secretion between untreated and omentin‐treated adipocytes were compared using a paired t‐test. Other potential upstream regulators and the overrepresentation in canonical pathways of omentin‐stimulated proteins were analysed using Ingenuity Pathway Analysis. Results The supernatant of adipocytes contained 3493 proteins, of which 140 were differentially secreted by both concentrations of omentin compared with untreated adipocytes. Among the most strongly increased proteins, tumour necrosis factor‐inducible gene 6 protein (TNFAIP6) was increased by 140‐fold in the supernatant. Omentin‐regulated proteins were overrepresented in seven canonical pathways including eukaryotic initiation factor 2 signalling, complement system, and inhibition of matrix metalloproteases. We further identified 25 other potential upstream activators of omentin‐regulated proteins, mainly pro‐inflammatory cytokines and transcription regulators including NFκB. Conclusions In differentiated human adipocytes, the release of the anti‐inflammatory TNFAIP6 might be part of a counterregulatory response to the pro‐inflammatory action of omentin. Omentin‐regulated proteins were overrepresented in pathways indicating cellular stress, a pro‐inflammatory environment and a crosstalk with other organs. Other potential activators of omentin‐regulated proteins point towards a central role of NFκB activation in the omentin‐induced secretory process.</description><subject>Adipocytes</subject><subject>Cardiovascular diseases</subject><subject>Cellular stress response</subject><subject>Complement activation</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Inflammation</subject><subject>Liquid chromatography</subject><subject>Mass spectroscopy</subject><subject>NF-κB protein</subject><subject>Obesity</subject><subject>omentin</subject><subject>Phenotypes</subject><subject>Protein folding</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Secretome</subject><subject>Signal transduction</subject><subject>Transcription</subject><subject>Tumor necrosis factor</subject><subject>Tumors</subject><issn>1520-7552</issn><issn>1520-7560</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kU1q3TAURkVoaZLXDrKBIuikGbxEkmXZziyk6Q-kBEI7NrJ03adgSY4kEzzrErqArC4ridz3mkGgIJC4HI4u34fQESUnlBB2qm0IJwWp-B46oCUj66oU5NXzu2T76DDGW0JIwQV_g_YLQpuaCnGAHq4tuGTc4-8_AX5Ng0yg8Rh8AuMiVt52xgGWyygjxvWDtFYmH2Y8bsD5NI-A703aYOnySeYlpfzkEoSd3HiHjcObyS64NqNXc4J4hs-3n3prVMweOczRxLfodS-HCO929wr9_Hz54-Lr-ur6y7eL86u1KuqarxUTXBZNIbqG657wutQlSME6pQXXoudaNYwp0sheaapqnuPpJG-agtcVq3WxQh-33rzD3QQxtdZEBcMgHfgptozmvChnOb8V-vACvfVTyPsulGAVY3VZZep4S6ngYwzQt2MwVoa5paRdKmuXytqlssy-3xmnzoJ-Jv91lIHTLXBvBpj_b2o_fb-5-at8AqXNp8g</recordid><startdate>201901</startdate><enddate>201901</enddate><creator>Niersmann, Corinna</creator><creator>Hauck, Stefanie M.</creator><creator>Kannenberg, Julia M.</creator><creator>Röhrig, Karin</creator><creator>Toerne, Christine</creator><creator>Roden, Michael</creator><creator>Herder, Christian</creator><creator>Carstensen‐Kirberg, Maren</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2050-093X</orcidid></search><sort><creationdate>201901</creationdate><title>Omentin‐regulated proteins combine a pro‐inflammatory phenotype with an anti‐inflammatory counterregulation in human adipocytes: A proteomics analysis</title><author>Niersmann, Corinna ; Hauck, Stefanie M. ; Kannenberg, Julia M. ; Röhrig, Karin ; Toerne, Christine ; Roden, Michael ; Herder, Christian ; Carstensen‐Kirberg, Maren</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3884-c264a3936b94df0485d5ea62bcd64d6f4dc922c09afcd1c84756ba499348728d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adipocytes</topic><topic>Cardiovascular diseases</topic><topic>Cellular stress response</topic><topic>Complement activation</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Inflammation</topic><topic>Liquid chromatography</topic><topic>Mass spectroscopy</topic><topic>NF-κB protein</topic><topic>Obesity</topic><topic>omentin</topic><topic>Phenotypes</topic><topic>Protein folding</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Secretome</topic><topic>Signal transduction</topic><topic>Transcription</topic><topic>Tumor necrosis factor</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Niersmann, Corinna</creatorcontrib><creatorcontrib>Hauck, Stefanie M.</creatorcontrib><creatorcontrib>Kannenberg, Julia M.</creatorcontrib><creatorcontrib>Röhrig, Karin</creatorcontrib><creatorcontrib>Toerne, Christine</creatorcontrib><creatorcontrib>Roden, Michael</creatorcontrib><creatorcontrib>Herder, Christian</creatorcontrib><creatorcontrib>Carstensen‐Kirberg, Maren</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes/metabolism research and reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Niersmann, Corinna</au><au>Hauck, Stefanie M.</au><au>Kannenberg, Julia M.</au><au>Röhrig, Karin</au><au>Toerne, Christine</au><au>Roden, Michael</au><au>Herder, Christian</au><au>Carstensen‐Kirberg, Maren</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Omentin‐regulated proteins combine a pro‐inflammatory phenotype with an anti‐inflammatory counterregulation in human adipocytes: A proteomics analysis</atitle><jtitle>Diabetes/metabolism research and reviews</jtitle><addtitle>Diabetes Metab Res Rev</addtitle><date>2019-01</date><risdate>2019</risdate><volume>35</volume><issue>1</issue><spage>e3074</spage><epage>n/a</epage><pages>e3074-n/a</pages><issn>1520-7552</issn><eissn>1520-7560</eissn><abstract>Aims Experimental and epidemiological studies reported controversial data on the role of omentin in type 2 diabetes and cardiovascular diseases. This study aimed to characterise the impact of omentin on the secretome of human adipocytes to analyse the enrichment of these proteins in metabolic and cellular signalling pathways underlying its physiological function. Material/methods Differentiated primary human adipocytes were treated without or with 500 or 2000 ng/mL omentin for 24 hours. The secretome was analysed by liquid chromatography coupled tandem‐mass spectrometry. Differences in protein secretion between untreated and omentin‐treated adipocytes were compared using a paired t‐test. Other potential upstream regulators and the overrepresentation in canonical pathways of omentin‐stimulated proteins were analysed using Ingenuity Pathway Analysis. Results The supernatant of adipocytes contained 3493 proteins, of which 140 were differentially secreted by both concentrations of omentin compared with untreated adipocytes. Among the most strongly increased proteins, tumour necrosis factor‐inducible gene 6 protein (TNFAIP6) was increased by 140‐fold in the supernatant. Omentin‐regulated proteins were overrepresented in seven canonical pathways including eukaryotic initiation factor 2 signalling, complement system, and inhibition of matrix metalloproteases. We further identified 25 other potential upstream activators of omentin‐regulated proteins, mainly pro‐inflammatory cytokines and transcription regulators including NFκB. Conclusions In differentiated human adipocytes, the release of the anti‐inflammatory TNFAIP6 might be part of a counterregulatory response to the pro‐inflammatory action of omentin. Omentin‐regulated proteins were overrepresented in pathways indicating cellular stress, a pro‐inflammatory environment and a crosstalk with other organs. Other potential activators of omentin‐regulated proteins point towards a central role of NFκB activation in the omentin‐induced secretory process.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30198166</pmid><doi>10.1002/dmrr.3074</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-2050-093X</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adipocytes
Cardiovascular diseases
Cellular stress response
Complement activation
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Inflammation
Liquid chromatography
Mass spectroscopy
NF-κB protein
Obesity
omentin
Phenotypes
Protein folding
Proteins
Proteomics
Secretome
Signal transduction
Transcription
Tumor necrosis factor
Tumors
title Omentin‐regulated proteins combine a pro‐inflammatory phenotype with an anti‐inflammatory counterregulation in human adipocytes: A proteomics analysis
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