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Suppression of Adipogenesis by Pathogenic Seipin Mutant Is Associated with Inflammatory Response
BACKGROUND: While pathogenic mutations in BSCL2/Seipin cause congenital generalized lipodystrophy, the underlying mechanism is largely unknown. In this study, we investigated whether and how the pathogenic missense A212P mutation of Seipin (Seipin-A212P) inhibits adipogenesis. METHODOLOGY/RESULTS: W...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592919/ https://www.ncbi.nlm.nih.gov/pubmed/23520483 http://dx.doi.org/10.1371/journal.pone.0057874 |
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author | Qiu, Wenjie Wee, Kenneth Takeda, Kosuke Lim, Xuemei Sugii, Shigeki Radda, George K. Han, Weiping |
author_facet | Qiu, Wenjie Wee, Kenneth Takeda, Kosuke Lim, Xuemei Sugii, Shigeki Radda, George K. Han, Weiping |
author_sort | Qiu, Wenjie |
collection | PubMed |
description | BACKGROUND: While pathogenic mutations in BSCL2/Seipin cause congenital generalized lipodystrophy, the underlying mechanism is largely unknown. In this study, we investigated whether and how the pathogenic missense A212P mutation of Seipin (Seipin-A212P) inhibits adipogenesis. METHODOLOGY/RESULTS: We analyzed gene expression and lipid accumulation in stable 3T3-L1 cell lines expressing wild type (3T3-WT), non-lipodystrophic mutants N88S (3T3-N88S) and S90L (3T3-S90L), or lipodystrophic mutant A212P Seipin (3T3-A212P). When treated with adipogenic cocktail, 3T3-WT, 3T3-N88S and 3T3-S90L cells exhibited proper differentiation into mature adipocytes, indistinguishable from control 3T3-L1 cells. In contrast, adipogenesis was significantly impaired in 3T3-A212P cells. The defective adipogenesis in 3T3-A212P cells could be partially rescued by either PPARγ agonist or PPARγ overexpression. Gene expression profiling by microarray revealed that inhibition of adipogenesis was associated with activation of inflammatory genes including IL-6 and iNOS. We further demonstrated that Seipin-A212P expression at pre-differentiation stages significantly activated inflammatory responses by using an inducible expression system. The inflammation-associated inhibition of adipogenesis could be rescued by treatment with anti-inflammatory agents. CONCLUSIONS: These results suggest that pathogenic Seipin-A212P inhibits adipogenesis and the inhibition is associated with activation of inflammatory pathways at pre-differentiation stages. Use of anti-inflammatory drugs may be a potential strategy for the treatment of lipodystrophy. |
format | Online Article Text |
id | pubmed-3592919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35929192013-03-21 Suppression of Adipogenesis by Pathogenic Seipin Mutant Is Associated with Inflammatory Response Qiu, Wenjie Wee, Kenneth Takeda, Kosuke Lim, Xuemei Sugii, Shigeki Radda, George K. Han, Weiping PLoS One Research Article BACKGROUND: While pathogenic mutations in BSCL2/Seipin cause congenital generalized lipodystrophy, the underlying mechanism is largely unknown. In this study, we investigated whether and how the pathogenic missense A212P mutation of Seipin (Seipin-A212P) inhibits adipogenesis. METHODOLOGY/RESULTS: We analyzed gene expression and lipid accumulation in stable 3T3-L1 cell lines expressing wild type (3T3-WT), non-lipodystrophic mutants N88S (3T3-N88S) and S90L (3T3-S90L), or lipodystrophic mutant A212P Seipin (3T3-A212P). When treated with adipogenic cocktail, 3T3-WT, 3T3-N88S and 3T3-S90L cells exhibited proper differentiation into mature adipocytes, indistinguishable from control 3T3-L1 cells. In contrast, adipogenesis was significantly impaired in 3T3-A212P cells. The defective adipogenesis in 3T3-A212P cells could be partially rescued by either PPARγ agonist or PPARγ overexpression. Gene expression profiling by microarray revealed that inhibition of adipogenesis was associated with activation of inflammatory genes including IL-6 and iNOS. We further demonstrated that Seipin-A212P expression at pre-differentiation stages significantly activated inflammatory responses by using an inducible expression system. The inflammation-associated inhibition of adipogenesis could be rescued by treatment with anti-inflammatory agents. CONCLUSIONS: These results suggest that pathogenic Seipin-A212P inhibits adipogenesis and the inhibition is associated with activation of inflammatory pathways at pre-differentiation stages. Use of anti-inflammatory drugs may be a potential strategy for the treatment of lipodystrophy. Public Library of Science 2013-03-08 /pmc/articles/PMC3592919/ /pubmed/23520483 http://dx.doi.org/10.1371/journal.pone.0057874 Text en © 2013 Qiu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Qiu, Wenjie Wee, Kenneth Takeda, Kosuke Lim, Xuemei Sugii, Shigeki Radda, George K. Han, Weiping Suppression of Adipogenesis by Pathogenic Seipin Mutant Is Associated with Inflammatory Response |
title | Suppression of Adipogenesis by Pathogenic Seipin Mutant Is Associated with Inflammatory Response |
title_full | Suppression of Adipogenesis by Pathogenic Seipin Mutant Is Associated with Inflammatory Response |
title_fullStr | Suppression of Adipogenesis by Pathogenic Seipin Mutant Is Associated with Inflammatory Response |
title_full_unstemmed | Suppression of Adipogenesis by Pathogenic Seipin Mutant Is Associated with Inflammatory Response |
title_short | Suppression of Adipogenesis by Pathogenic Seipin Mutant Is Associated with Inflammatory Response |
title_sort | suppression of adipogenesis by pathogenic seipin mutant is associated with inflammatory response |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592919/ https://www.ncbi.nlm.nih.gov/pubmed/23520483 http://dx.doi.org/10.1371/journal.pone.0057874 |
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