Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation.
Geldanamycin derivatives are benzoquinone ansamycin antibiotics that bind to Hsp90 and alter its function. The alteration of Hsp90 activity limits some cellular hormonal responses by inhibiting nuclear receptors activation. The nuclear receptors activity, such as PPARγ, the mineralocorticoid and glu...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0094127&type=printable |
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| author | Sébastien Desarzens Wan-Hui Liao Caterina Mammi Massimiliano Caprio Nourdine Faresse |
| author_facet | Sébastien Desarzens Wan-Hui Liao Caterina Mammi Massimiliano Caprio Nourdine Faresse |
| author_sort | Sébastien Desarzens |
| collection | DOAJ |
| description | Geldanamycin derivatives are benzoquinone ansamycin antibiotics that bind to Hsp90 and alter its function. The alteration of Hsp90 activity limits some cellular hormonal responses by inhibiting nuclear receptors activation. The nuclear receptors activity, such as PPARγ, the mineralocorticoid and glucocorticoid receptors (MR and GR) play a critical role in the conversion of preadipocytes to mature adipocytes. Given the importance of these nuclear receptors for adipogenesis, we investigated the effects of geldanamycin analogues (GA) on adipocyte differentiation and function. We found that early exposure of preadipocyte cells to GA inhibited their conversion into mature adipocytes by inhibiting the adipogenic transcriptional program and lipid droplets accumulation. Furthermore, GA altered the adipokines secretion profile of mature adipocyte. The anti-adipogenic effect of GA was also confirmed in mice fed a high fat diet. Biochemical analysis revealed that anti-adipogenic effects of geldanamycin analogues may result from the simultaneous inhibition of MR, GR and PPARγ activity. Taken together, our observations lead us to propose Hsp90 as a potent target for drug development in the control of obesity and its related metabolic complications. |
| format | Article |
| id | doaj-art-b8eb59a4d5944eb2a01d32828ffbd93a |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-b8eb59a4d5944eb2a01d32828ffbd93a2025-08-20T03:00:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9412710.1371/journal.pone.0094127Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation.Sébastien DesarzensWan-Hui LiaoCaterina MammiMassimiliano CaprioNourdine FaresseGeldanamycin derivatives are benzoquinone ansamycin antibiotics that bind to Hsp90 and alter its function. The alteration of Hsp90 activity limits some cellular hormonal responses by inhibiting nuclear receptors activation. The nuclear receptors activity, such as PPARγ, the mineralocorticoid and glucocorticoid receptors (MR and GR) play a critical role in the conversion of preadipocytes to mature adipocytes. Given the importance of these nuclear receptors for adipogenesis, we investigated the effects of geldanamycin analogues (GA) on adipocyte differentiation and function. We found that early exposure of preadipocyte cells to GA inhibited their conversion into mature adipocytes by inhibiting the adipogenic transcriptional program and lipid droplets accumulation. Furthermore, GA altered the adipokines secretion profile of mature adipocyte. The anti-adipogenic effect of GA was also confirmed in mice fed a high fat diet. Biochemical analysis revealed that anti-adipogenic effects of geldanamycin analogues may result from the simultaneous inhibition of MR, GR and PPARγ activity. Taken together, our observations lead us to propose Hsp90 as a potent target for drug development in the control of obesity and its related metabolic complications.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0094127&type=printable |
| spellingShingle | Sébastien Desarzens Wan-Hui Liao Caterina Mammi Massimiliano Caprio Nourdine Faresse Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation. PLoS ONE |
| title | Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation. |
| title_full | Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation. |
| title_fullStr | Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation. |
| title_full_unstemmed | Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation. |
| title_short | Hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation. |
| title_sort | hsp90 blockers inhibit adipocyte differentiation and fat mass accumulation |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0094127&type=printable |
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