Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis
<p><strong>Background:</strong><br /> Bone morphogenetic proteins (BMPs) regulate adipogenesis but it is not clear whether they influence regional adipose tissue (AT) development in humans.</p><br /> <p><strong>Objective:</strong><br /> To...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2019
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| _version_ | 1797099763263340544 |
|---|---|
| author | Denton, N Eghleilib, M Al-Sharifi, S Todorčević, M Neville, M Loh, N Drakesmith, A Karpe, F Pinnick, K |
| author_facet | Denton, N Eghleilib, M Al-Sharifi, S Todorčević, M Neville, M Loh, N Drakesmith, A Karpe, F Pinnick, K |
| author_sort | Denton, N |
| collection | OXFORD |
| description | <p><strong>Background:</strong><br />
Bone morphogenetic proteins (BMPs) regulate adipogenesis but it is not clear whether they influence regional adipose tissue (AT) development in humans.</p><br />
<p><strong>Objective:</strong><br />
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.</p><br />
<p><strong>Methods:</strong><br />
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.</p><br />
<p><strong>Results:</strong><br />
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).</p><br />
<p><strong>Conclusions:</strong><br />
These data implicate BMP2-SMAD1/5/8 signalling in depot-specific preadipocyte development and abdominal AT expansion in humans.</p> |
| first_indexed | 2024-03-07T05:28:13Z |
| format | Journal article |
| id | oxford-uuid:e149e90b-713b-4370-a739-32243d22a56e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:28:13Z |
| publishDate | 2019 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:e149e90b-713b-4370-a739-32243d22a56e2022-03-27T09:53:28ZBone morphogenetic protein 2 is a depot-specific regulator of human adipogenesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e149e90b-713b-4370-a739-32243d22a56eEnglishSymplectic Elements at OxfordSpringer Nature2019Denton, NEghleilib, MAl-Sharifi, STodorčević, MNeville, MLoh, NDrakesmith, AKarpe, FPinnick, K<p><strong>Background:</strong><br /> Bone morphogenetic proteins (BMPs) regulate adipogenesis but it is not clear whether they influence regional adipose tissue (AT) development in humans.</p><br /> <p><strong>Objective:</strong><br /> 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.</p><br /> <p><strong>Methods:</strong><br /> 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.</p><br /> <p><strong>Results:</strong><br /> 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).</p><br /> <p><strong>Conclusions:</strong><br /> These data implicate BMP2-SMAD1/5/8 signalling in depot-specific preadipocyte development and abdominal AT expansion in humans.</p> |
| spellingShingle | Denton, N Eghleilib, M Al-Sharifi, S Todorčević, M Neville, M Loh, N Drakesmith, A Karpe, F Pinnick, K Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis |
| title | Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis |
| title_full | Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis |
| title_fullStr | Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis |
| title_full_unstemmed | Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis |
| title_short | Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis |
| title_sort | bone morphogenetic protein 2 is a depot specific regulator of human adipogenesis |
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