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 |
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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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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><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 & Sons, Ltd.</rights><rights>2019 John Wiley & 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 & 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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