Loss of Mfn1 but not Mfn2 enhances adipogenesis.
<h4>Objective</h4>A biallelic missense mutation in mitofusin 2 (MFN2) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles in adipocyte differentiation, growth and/or survival. In this study,...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0306243 |
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| author | Jake P Mann Luis Carlos Tábara Satish Patel Pushpa Pushpa Anna Alvarez-Guaita Liang Dong Afreen Haider Koini Lim Panna Tandon Fabio Scurria James E N Minchin Stephen O'Rahilly S Daniel J Fazakerley Julien Prudent Robert K Semple David B Savage |
| author_facet | Jake P Mann Luis Carlos Tábara Satish Patel Pushpa Pushpa Anna Alvarez-Guaita Liang Dong Afreen Haider Koini Lim Panna Tandon Fabio Scurria James E N Minchin Stephen O'Rahilly S Daniel J Fazakerley Julien Prudent Robert K Semple David B Savage |
| author_sort | Jake P Mann |
| collection | DOAJ |
| description | <h4>Objective</h4>A biallelic missense mutation in mitofusin 2 (MFN2) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles in adipocyte differentiation, growth and/or survival. In this study, we aimed to document the impact of loss of mitofusin 1 (Mfn1) or 2 (Mfn2) on adipogenesis in cultured cells.<h4>Methods</h4>We characterised adipocyte differentiation of wildtype (WT), Mfn1-/- and Mfn2-/- mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes in which Mfn1 or 2 levels were reduced using siRNA.<h4>Results</h4>Mfn1-/- MEFs displayed striking fragmentation of the mitochondrial network, with surprisingly enhanced propensity to differentiate into adipocytes, as assessed by lipid accumulation, expression of adipocyte markers (Plin1, Fabp4, Glut4, Adipoq), and insulin-stimulated glucose uptake. RNA sequencing revealed a corresponding pro-adipogenic transcriptional profile including Pparg upregulation. Mfn2-/- MEFs also had a disrupted mitochondrial morphology, but in contrast to Mfn1-/- MEFs they showed reduced expression of adipocyte markers. Mfn1 and Mfn2 siRNA mediated knockdown studies in 3T3-L1 adipocytes generally replicated these findings.<h4>Conclusions</h4>Loss of Mfn1 but not Mfn2 in cultured pre-adipocyte models is pro-adipogenic. This suggests distinct, non-redundant roles for the two mitofusin orthologues in adipocyte differentiation. |
| format | Article |
| id | doaj-art-72afcdd7e9934e0a8cb6a18e408e8c7a |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-72afcdd7e9934e0a8cb6a18e408e8c7a2025-01-08T05:32:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e030624310.1371/journal.pone.0306243Loss of Mfn1 but not Mfn2 enhances adipogenesis.Jake P MannLuis Carlos TábaraSatish PatelPushpa PushpaAnna Alvarez-GuaitaLiang DongAfreen HaiderKoini LimPanna TandonFabio ScurriaJames E N MinchinStephen O'Rahilly SDaniel J FazakerleyJulien PrudentRobert K SempleDavid B Savage<h4>Objective</h4>A biallelic missense mutation in mitofusin 2 (MFN2) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles in adipocyte differentiation, growth and/or survival. In this study, we aimed to document the impact of loss of mitofusin 1 (Mfn1) or 2 (Mfn2) on adipogenesis in cultured cells.<h4>Methods</h4>We characterised adipocyte differentiation of wildtype (WT), Mfn1-/- and Mfn2-/- mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes in which Mfn1 or 2 levels were reduced using siRNA.<h4>Results</h4>Mfn1-/- MEFs displayed striking fragmentation of the mitochondrial network, with surprisingly enhanced propensity to differentiate into adipocytes, as assessed by lipid accumulation, expression of adipocyte markers (Plin1, Fabp4, Glut4, Adipoq), and insulin-stimulated glucose uptake. RNA sequencing revealed a corresponding pro-adipogenic transcriptional profile including Pparg upregulation. Mfn2-/- MEFs also had a disrupted mitochondrial morphology, but in contrast to Mfn1-/- MEFs they showed reduced expression of adipocyte markers. Mfn1 and Mfn2 siRNA mediated knockdown studies in 3T3-L1 adipocytes generally replicated these findings.<h4>Conclusions</h4>Loss of Mfn1 but not Mfn2 in cultured pre-adipocyte models is pro-adipogenic. This suggests distinct, non-redundant roles for the two mitofusin orthologues in adipocyte differentiation.https://doi.org/10.1371/journal.pone.0306243 |
| spellingShingle | Jake P Mann Luis Carlos Tábara Satish Patel Pushpa Pushpa Anna Alvarez-Guaita Liang Dong Afreen Haider Koini Lim Panna Tandon Fabio Scurria James E N Minchin Stephen O'Rahilly S Daniel J Fazakerley Julien Prudent Robert K Semple David B Savage Loss of Mfn1 but not Mfn2 enhances adipogenesis. PLoS ONE |
| title | Loss of Mfn1 but not Mfn2 enhances adipogenesis. |
| title_full | Loss of Mfn1 but not Mfn2 enhances adipogenesis. |
| title_fullStr | Loss of Mfn1 but not Mfn2 enhances adipogenesis. |
| title_full_unstemmed | Loss of Mfn1 but not Mfn2 enhances adipogenesis. |
| title_short | Loss of Mfn1 but not Mfn2 enhances adipogenesis. |
| title_sort | loss of mfn1 but not mfn2 enhances adipogenesis |
| url | https://doi.org/10.1371/journal.pone.0306243 |
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