Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis
Background Bone morphogenetic proteins (BMPs) regulate adipogenesis but it is not clear whether they influence regional adipose tissue (AT) development in humans. Objective To characterise BMP2 expression, BMP2-SMAD1/5/8 signalling, and BMP2′s potential effect on proliferation and adipogenesis in hu...
Gespeichert in:
| Veröffentlicht in: | International Journal of Obesity 2019-12, Vol.43 (12), p.2458-2468 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2468 |
|---|---|
| container_issue | 12 |
| container_start_page | 2458 |
| container_title | International Journal of Obesity |
| container_volume | 43 |
| creator | Denton, Nathan F. Eghleilib, Mohamed Al-Sharifi, Sama Todorčević, Marijana Neville, Matt J. Loh, Nellie Drakesmith, Alexander Karpe, Fredrik Pinnick, Katherine E. |
| description | Background
Bone morphogenetic proteins (BMPs) regulate adipogenesis but it is not clear whether they influence regional adipose tissue (AT) development in humans.
Objective
To characterise
BMP2
expression, BMP2-SMAD1/5/8 signalling, and BMP2′s potential effect on proliferation and adipogenesis in human subcutaneous abdominal and gluteal AT and its constituent preadipocytes.
Methods
BMP2
expression was measured in whole AT and immortalised preadipocytes via qPCR and Western blot; secreted/circulating BMP2 was measured by ELISA. The effect of BMP2 on preadipocyte proliferation was evaluated using a fluorescent assay. BMP2′s effect on adipogenesis in immortalised preadipocytes was determined via qPCR of adipogenic markers and cellular triacylglycerol (TAG) accumulation. BMP2-SMAD1/5/8 signalling was assessed in immortalised preadipocytes via Western blot and qPCR of
ID1
expression.
Results
BMP2 was expressed and released by abdominal and gluteal AT and preadipocytes. Exogenous BMP2 dose dependently promoted adipogenesis in abdominal preadipocytes only; 50 ng/ml BMP2 increased
PPARG2
expression (10-fold compared to vehicle,
p
|
| doi_str_mv | 10.1038/s41366-019-0421-1 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6892741</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A607607979</galeid><sourcerecordid>A607607979</sourcerecordid><originalsourceid>FETCH-LOGICAL-c535t-20c66f46c0b0199f661c473dc086f7e9a03a014f0531ddb3b814a31fb151c213</originalsourceid><addsrcrecordid>eNp1kt1r1jAUxoMo7nX6B3gjBcG7zpPv9kaYY37AQC92H9I0aTPapCbtwP_evHvntheUBAI5v-ch58lB6C2GMwy0-ZgZpkLUgNsaGME1foZ2mElRc9bK52gHFGQNXPAT9CrnGwDgHMhLdEIxJayR7Q79_ByDreaYljEONtjVm2pJcbU-VKTyudJVb5e41nmxxrtSTXbYJr3GVEVXjdusQ6V7v9yps8-v0Qunp2zf3J-n6PrL5fXFt_rqx9fvF-dXteGUrzUBI4RjwkBXnt86IbBhkvYGGuGkbTVQDZg54BT3fUe7BjNNseswx4Zgeoo-HWyXrZttb2xYk57Ukvys028VtVfHleBHNcRbJZqWSLY3eH9vkOKvzeZV3cQthfJkRSjBoqRD-CM16MkqH1wsZmb22ahzAbLsVraFOvsHVVZvZ29KwM6X-yPBhyeC0eppHXOcttXHkI9BfABNijkn6x46xKD2M6AOM6BKiGo_A2rf2bun0Two_n56AcgByKUUBpseW_-_6x9NI7pv</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2321687925</pqid></control><display><type>article</type><title>Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis</title><source>Nature Publishing Group</source><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Denton, Nathan F. ; Eghleilib, Mohamed ; Al-Sharifi, Sama ; Todorčević, Marijana ; Neville, Matt J. ; Loh, Nellie ; Drakesmith, Alexander ; Karpe, Fredrik ; Pinnick, Katherine E.</creator><creatorcontrib>Denton, Nathan F. ; Eghleilib, Mohamed ; Al-Sharifi, Sama ; Todorčević, Marijana ; Neville, Matt J. ; Loh, Nellie ; Drakesmith, Alexander ; Karpe, Fredrik ; Pinnick, Katherine E.</creatorcontrib><description><![CDATA[Background
Bone morphogenetic proteins (BMPs) regulate adipogenesis but it is not clear whether they influence regional adipose tissue (AT) development in humans.
Objective
To characterise
BMP2
expression, BMP2-SMAD1/5/8 signalling, and BMP2′s potential effect on proliferation and adipogenesis in human subcutaneous abdominal and gluteal AT and its constituent preadipocytes.
Methods
BMP2
expression was measured in whole AT and immortalised preadipocytes via qPCR and Western blot; secreted/circulating BMP2 was measured by ELISA. The effect of BMP2 on preadipocyte proliferation was evaluated using a fluorescent assay. BMP2′s effect on adipogenesis in immortalised preadipocytes was determined via qPCR of adipogenic markers and cellular triacylglycerol (TAG) accumulation. BMP2-SMAD1/5/8 signalling was assessed in immortalised preadipocytes via Western blot and qPCR of
ID1
expression.
Results
BMP2 was expressed and released by abdominal and gluteal AT and preadipocytes. Exogenous BMP2 dose dependently promoted adipogenesis in abdominal preadipocytes only; 50 ng/ml BMP2 increased
PPARG2
expression (10-fold compared to vehicle,
p
< 0.001) and TAG accumulation (3-fold compared to vehicle;
p
< 0.001). BMP2 stimulated SMAD1/5/8 phosphorylation and
ID1
expression in abdominal and gluteal preadipocytes but this was blocked by 500 nM K02288, a type 1 BMP receptor inhibitor (
p
< 0.001). Co-administration of 500 nM K02288 also inhibited the pro-adipogenic effect of 50 ng/ml BMP2 in abdominal cells; >90% inhibition of TAG accumulation (
p
< 0.001) and ~50% inhibition of
PPARG2
expression (
p
< 0.001). The endogenous iron regulator erythroferrone reduced BMP2-SMAD1/5/8 signalling by ~30% specifically in subcutaneous abdominal preadipocytes (
p
< 0.01), suggesting it plays a role in restricting the expansion of the body’s largest AT depot during energy deficiency. Additionally, a waist-hip ratio-increasing common polymorphism near
BMP2
is an eQTL associated with ~15% lower
BMP2
expression in abdominal and gluteal AT (
p
< 0.05) as well as altered adipocyte size in male abdominal AT (
p
< 0.05).
Conclusions
These data implicate BMP2-SMAD1/5/8 signalling in depot-specific preadipocyte development and abdominal AT expansion in humans.]]></description><identifier>ISSN: 0307-0565</identifier><identifier>EISSN: 1476-5497</identifier><identifier>DOI: 10.1038/s41366-019-0421-1</identifier><identifier>PMID: 31324879</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 38/77 ; 631/443 ; 631/80 ; 82/80 ; 96/95 ; Abdomen ; Accumulation ; Adipocytes - cytology ; Adipocytes - metabolism ; Adipogenesis ; Adipogenesis - physiology ; Adipose tissue ; Adipose Tissue - cytology ; Adipose Tissue - metabolism ; Adipose tissues ; Adult ; Aged ; Body Mass Index ; Bone morphogenetic protein 2 ; Bone Morphogenetic Protein 2 - metabolism ; Bone morphogenetic proteins ; Cell Proliferation - physiology ; Cells, Cultured ; Enzyme-linked immunosorbent assay ; Epidemiology ; Ethylenediaminetetraacetic acid ; Female ; Fluorescence ; Health Promotion and Disease Prevention ; Hip ; Humans ; Id1 protein ; Internal Medicine ; Iron constituents ; Male ; Measurement methods ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Middle Aged ; Phosphorylation ; Polymorphism ; Preadipocytes ; Proteins ; Public Health ; Regional development ; Signal Transduction - physiology ; Signaling ; Smad Proteins, Receptor-Regulated - metabolism ; Triglycerides</subject><ispartof>International Journal of Obesity, 2019-12, Vol.43 (12), p.2458-2468</ispartof><rights>The Author(s) 2019. This article is published with open access. 2019</rights><rights>COPYRIGHT 2019 Nature Publishing Group</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c535t-20c66f46c0b0199f661c473dc086f7e9a03a014f0531ddb3b814a31fb151c213</citedby><cites>FETCH-LOGICAL-c535t-20c66f46c0b0199f661c473dc086f7e9a03a014f0531ddb3b814a31fb151c213</cites><orcidid>0000-0002-2422-248X ; 0000-0002-6004-5433 ; 0000-0002-8503-6103</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31324879$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Denton, Nathan F.</creatorcontrib><creatorcontrib>Eghleilib, Mohamed</creatorcontrib><creatorcontrib>Al-Sharifi, Sama</creatorcontrib><creatorcontrib>Todorčević, Marijana</creatorcontrib><creatorcontrib>Neville, Matt J.</creatorcontrib><creatorcontrib>Loh, Nellie</creatorcontrib><creatorcontrib>Drakesmith, Alexander</creatorcontrib><creatorcontrib>Karpe, Fredrik</creatorcontrib><creatorcontrib>Pinnick, Katherine E.</creatorcontrib><title>Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis</title><title>International Journal of Obesity</title><addtitle>Int J Obes</addtitle><addtitle>Int J Obes (Lond)</addtitle><description><![CDATA[Background
Bone morphogenetic proteins (BMPs) regulate adipogenesis but it is not clear whether they influence regional adipose tissue (AT) development in humans.
Objective
To characterise
BMP2
expression, BMP2-SMAD1/5/8 signalling, and BMP2′s potential effect on proliferation and adipogenesis in human subcutaneous abdominal and gluteal AT and its constituent preadipocytes.
Methods
BMP2
expression was measured in whole AT and immortalised preadipocytes via qPCR and Western blot; secreted/circulating BMP2 was measured by ELISA. The effect of BMP2 on preadipocyte proliferation was evaluated using a fluorescent assay. BMP2′s effect on adipogenesis in immortalised preadipocytes was determined via qPCR of adipogenic markers and cellular triacylglycerol (TAG) accumulation. BMP2-SMAD1/5/8 signalling was assessed in immortalised preadipocytes via Western blot and qPCR of
ID1
expression.
Results
BMP2 was expressed and released by abdominal and gluteal AT and preadipocytes. Exogenous BMP2 dose dependently promoted adipogenesis in abdominal preadipocytes only; 50 ng/ml BMP2 increased
PPARG2
expression (10-fold compared to vehicle,
p
< 0.001) and TAG accumulation (3-fold compared to vehicle;
p
< 0.001). BMP2 stimulated SMAD1/5/8 phosphorylation and
ID1
expression in abdominal and gluteal preadipocytes but this was blocked by 500 nM K02288, a type 1 BMP receptor inhibitor (
p
< 0.001). Co-administration of 500 nM K02288 also inhibited the pro-adipogenic effect of 50 ng/ml BMP2 in abdominal cells; >90% inhibition of TAG accumulation (
p
< 0.001) and ~50% inhibition of
PPARG2
expression (
p
< 0.001). The endogenous iron regulator erythroferrone reduced BMP2-SMAD1/5/8 signalling by ~30% specifically in subcutaneous abdominal preadipocytes (
p
< 0.01), suggesting it plays a role in restricting the expansion of the body’s largest AT depot during energy deficiency. Additionally, a waist-hip ratio-increasing common polymorphism near
BMP2
is an eQTL associated with ~15% lower
BMP2
expression in abdominal and gluteal AT (
p
< 0.05) as well as altered adipocyte size in male abdominal AT (
p
< 0.05).
Conclusions
These data implicate BMP2-SMAD1/5/8 signalling in depot-specific preadipocyte development and abdominal AT expansion in humans.]]></description><subject>13/106</subject><subject>38/77</subject><subject>631/443</subject><subject>631/80</subject><subject>82/80</subject><subject>96/95</subject><subject>Abdomen</subject><subject>Accumulation</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - metabolism</subject><subject>Adipogenesis</subject><subject>Adipogenesis - physiology</subject><subject>Adipose tissue</subject><subject>Adipose Tissue - cytology</subject><subject>Adipose Tissue - metabolism</subject><subject>Adipose tissues</subject><subject>Adult</subject><subject>Aged</subject><subject>Body Mass Index</subject><subject>Bone morphogenetic protein 2</subject><subject>Bone Morphogenetic Protein 2 - metabolism</subject><subject>Bone morphogenetic proteins</subject><subject>Cell Proliferation - physiology</subject><subject>Cells, Cultured</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Epidemiology</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Female</subject><subject>Fluorescence</subject><subject>Health Promotion and Disease Prevention</subject><subject>Hip</subject><subject>Humans</subject><subject>Id1 protein</subject><subject>Internal Medicine</subject><subject>Iron constituents</subject><subject>Male</subject><subject>Measurement methods</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Phosphorylation</subject><subject>Polymorphism</subject><subject>Preadipocytes</subject><subject>Proteins</subject><subject>Public Health</subject><subject>Regional development</subject><subject>Signal Transduction - physiology</subject><subject>Signaling</subject><subject>Smad Proteins, Receptor-Regulated - metabolism</subject><subject>Triglycerides</subject><issn>0307-0565</issn><issn>1476-5497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><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>eNp1kt1r1jAUxoMo7nX6B3gjBcG7zpPv9kaYY37AQC92H9I0aTPapCbtwP_evHvntheUBAI5v-ch58lB6C2GMwy0-ZgZpkLUgNsaGME1foZ2mElRc9bK52gHFGQNXPAT9CrnGwDgHMhLdEIxJayR7Q79_ByDreaYljEONtjVm2pJcbU-VKTyudJVb5e41nmxxrtSTXbYJr3GVEVXjdusQ6V7v9yps8-v0Qunp2zf3J-n6PrL5fXFt_rqx9fvF-dXteGUrzUBI4RjwkBXnt86IbBhkvYGGuGkbTVQDZg54BT3fUe7BjNNseswx4Zgeoo-HWyXrZttb2xYk57Ukvys028VtVfHleBHNcRbJZqWSLY3eH9vkOKvzeZV3cQthfJkRSjBoqRD-CM16MkqH1wsZmb22ahzAbLsVraFOvsHVVZvZ29KwM6X-yPBhyeC0eppHXOcttXHkI9BfABNijkn6x46xKD2M6AOM6BKiGo_A2rf2bun0Two_n56AcgByKUUBpseW_-_6x9NI7pv</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Denton, Nathan F.</creator><creator>Eghleilib, Mohamed</creator><creator>Al-Sharifi, Sama</creator><creator>Todorčević, Marijana</creator><creator>Neville, Matt J.</creator><creator>Loh, Nellie</creator><creator>Drakesmith, Alexander</creator><creator>Karpe, Fredrik</creator><creator>Pinnick, Katherine E.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>7T2</scope><scope>7TK</scope><scope>7TS</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2422-248X</orcidid><orcidid>https://orcid.org/0000-0002-6004-5433</orcidid><orcidid>https://orcid.org/0000-0002-8503-6103</orcidid></search><sort><creationdate>20191201</creationdate><title>Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis</title><author>Denton, Nathan F. ; Eghleilib, Mohamed ; Al-Sharifi, Sama ; Todorčević, Marijana ; Neville, Matt J. ; Loh, Nellie ; Drakesmith, Alexander ; Karpe, Fredrik ; Pinnick, Katherine E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c535t-20c66f46c0b0199f661c473dc086f7e9a03a014f0531ddb3b814a31fb151c213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/106</topic><topic>38/77</topic><topic>631/443</topic><topic>631/80</topic><topic>82/80</topic><topic>96/95</topic><topic>Abdomen</topic><topic>Accumulation</topic><topic>Adipocytes - cytology</topic><topic>Adipocytes - metabolism</topic><topic>Adipogenesis</topic><topic>Adipogenesis - physiology</topic><topic>Adipose tissue</topic><topic>Adipose Tissue - cytology</topic><topic>Adipose Tissue - metabolism</topic><topic>Adipose tissues</topic><topic>Adult</topic><topic>Aged</topic><topic>Body Mass Index</topic><topic>Bone morphogenetic protein 2</topic><topic>Bone Morphogenetic Protein 2 - metabolism</topic><topic>Bone morphogenetic proteins</topic><topic>Cell Proliferation - physiology</topic><topic>Cells, Cultured</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Epidemiology</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Female</topic><topic>Fluorescence</topic><topic>Health Promotion and Disease Prevention</topic><topic>Hip</topic><topic>Humans</topic><topic>Id1 protein</topic><topic>Internal Medicine</topic><topic>Iron constituents</topic><topic>Male</topic><topic>Measurement methods</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Phosphorylation</topic><topic>Polymorphism</topic><topic>Preadipocytes</topic><topic>Proteins</topic><topic>Public Health</topic><topic>Regional development</topic><topic>Signal Transduction - physiology</topic><topic>Signaling</topic><topic>Smad Proteins, Receptor-Regulated - metabolism</topic><topic>Triglycerides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Denton, Nathan F.</creatorcontrib><creatorcontrib>Eghleilib, Mohamed</creatorcontrib><creatorcontrib>Al-Sharifi, Sama</creatorcontrib><creatorcontrib>Todorčević, Marijana</creatorcontrib><creatorcontrib>Neville, Matt J.</creatorcontrib><creatorcontrib>Loh, Nellie</creatorcontrib><creatorcontrib>Drakesmith, Alexander</creatorcontrib><creatorcontrib>Karpe, Fredrik</creatorcontrib><creatorcontrib>Pinnick, Katherine E.</creatorcontrib><collection>Springer_OA刊</collection><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>Health and Safety Science Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Agricultural Science Collection</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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)</collection><collection>ProQuest Central</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Psychology Database</collection><collection>Biological 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 One Psychology</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International Journal of Obesity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Denton, Nathan F.</au><au>Eghleilib, Mohamed</au><au>Al-Sharifi, Sama</au><au>Todorčević, Marijana</au><au>Neville, Matt J.</au><au>Loh, Nellie</au><au>Drakesmith, Alexander</au><au>Karpe, Fredrik</au><au>Pinnick, Katherine E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis</atitle><jtitle>International Journal of Obesity</jtitle><stitle>Int J Obes</stitle><addtitle>Int J Obes (Lond)</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>43</volume><issue>12</issue><spage>2458</spage><epage>2468</epage><pages>2458-2468</pages><issn>0307-0565</issn><eissn>1476-5497</eissn><abstract><![CDATA[Background
Bone morphogenetic proteins (BMPs) regulate adipogenesis but it is not clear whether they influence regional adipose tissue (AT) development in humans.
Objective
To characterise
BMP2
expression, BMP2-SMAD1/5/8 signalling, and BMP2′s potential effect on proliferation and adipogenesis in human subcutaneous abdominal and gluteal AT and its constituent preadipocytes.
Methods
BMP2
expression was measured in whole AT and immortalised preadipocytes via qPCR and Western blot; secreted/circulating BMP2 was measured by ELISA. The effect of BMP2 on preadipocyte proliferation was evaluated using a fluorescent assay. BMP2′s effect on adipogenesis in immortalised preadipocytes was determined via qPCR of adipogenic markers and cellular triacylglycerol (TAG) accumulation. BMP2-SMAD1/5/8 signalling was assessed in immortalised preadipocytes via Western blot and qPCR of
ID1
expression.
Results
BMP2 was expressed and released by abdominal and gluteal AT and preadipocytes. Exogenous BMP2 dose dependently promoted adipogenesis in abdominal preadipocytes only; 50 ng/ml BMP2 increased
PPARG2
expression (10-fold compared to vehicle,
p
< 0.001) and TAG accumulation (3-fold compared to vehicle;
p
< 0.001). BMP2 stimulated SMAD1/5/8 phosphorylation and
ID1
expression in abdominal and gluteal preadipocytes but this was blocked by 500 nM K02288, a type 1 BMP receptor inhibitor (
p
< 0.001). Co-administration of 500 nM K02288 also inhibited the pro-adipogenic effect of 50 ng/ml BMP2 in abdominal cells; >90% inhibition of TAG accumulation (
p
< 0.001) and ~50% inhibition of
PPARG2
expression (
p
< 0.001). The endogenous iron regulator erythroferrone reduced BMP2-SMAD1/5/8 signalling by ~30% specifically in subcutaneous abdominal preadipocytes (
p
< 0.01), suggesting it plays a role in restricting the expansion of the body’s largest AT depot during energy deficiency. Additionally, a waist-hip ratio-increasing common polymorphism near
BMP2
is an eQTL associated with ~15% lower
BMP2
expression in abdominal and gluteal AT (
p
< 0.05) as well as altered adipocyte size in male abdominal AT (
p
< 0.05).
Conclusions
These data implicate BMP2-SMAD1/5/8 signalling in depot-specific preadipocyte development and abdominal AT expansion in humans.]]></abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31324879</pmid><doi>10.1038/s41366-019-0421-1</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2422-248X</orcidid><orcidid>https://orcid.org/0000-0002-6004-5433</orcidid><orcidid>https://orcid.org/0000-0002-8503-6103</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0307-0565 |
| ispartof | International Journal of Obesity, 2019-12, Vol.43 (12), p.2458-2468 |
| issn | 0307-0565 1476-5497 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6892741 |
| source | Nature Publishing Group; MEDLINE; Alma/SFX Local Collection |
| subjects | 13/106 38/77 631/443 631/80 82/80 96/95 Abdomen Accumulation Adipocytes - cytology Adipocytes - metabolism Adipogenesis Adipogenesis - physiology Adipose tissue Adipose Tissue - cytology Adipose Tissue - metabolism Adipose tissues Adult Aged Body Mass Index Bone morphogenetic protein 2 Bone Morphogenetic Protein 2 - metabolism Bone morphogenetic proteins Cell Proliferation - physiology Cells, Cultured Enzyme-linked immunosorbent assay Epidemiology Ethylenediaminetetraacetic acid Female Fluorescence Health Promotion and Disease Prevention Hip Humans Id1 protein Internal Medicine Iron constituents Male Measurement methods Medicine Medicine & Public Health Metabolic Diseases Middle Aged Phosphorylation Polymorphism Preadipocytes Proteins Public Health Regional development Signal Transduction - physiology Signaling Smad Proteins, Receptor-Regulated - metabolism Triglycerides |
| title | Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T05%3A14%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Bone%20morphogenetic%20protein%202%20is%20a%20depot-specific%20regulator%20of%20human%20adipogenesis&rft.jtitle=International%20Journal%20of%20Obesity&rft.au=Denton,%20Nathan%20F.&rft.date=2019-12-01&rft.volume=43&rft.issue=12&rft.spage=2458&rft.epage=2468&rft.pages=2458-2468&rft.issn=0307-0565&rft.eissn=1476-5497&rft_id=info:doi/10.1038/s41366-019-0421-1&rft_dat=%3Cgale_pubme%3EA607607979%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2321687925&rft_id=info:pmid/31324879&rft_galeid=A607607979&rfr_iscdi=true |