PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting.
FOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1 expression in muscle wasting are poorly understood. We hypothesized that the transcription factor peroxisome proliferator-activated receptor β/δ...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3605288?pdf=render |
| _version_ | 1818923828604043264 |
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| author | Estibaliz Castillero Nima Alamdari Zaira Aversa Aniket Gurav Per-Olof Hasselgren |
| author_facet | Estibaliz Castillero Nima Alamdari Zaira Aversa Aniket Gurav Per-Olof Hasselgren |
| author_sort | Estibaliz Castillero |
| collection | DOAJ |
| description | FOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1 expression in muscle wasting are poorly understood. We hypothesized that the transcription factor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) upregulates muscle FOXO1 expression and activity with a downstream upregulation of atrogin-1 and MuRF1 expression during sepsis and glucocorticoid treatment and that inhibition of PPARβ/δ activity can prevent muscle wasting. We found that activation of PPARβ/δ in cultured myotubes increased FOXO1 activity, atrogin-1 and MuRF1 expression, protein degradation and myotube atrophy. Treatment of myotubes with dexamethasone increased PPARβ/δ expression and activity. Dexamethasone-induced FOXO1 activation and atrogin-1 and MuRF1 expression, protein degradation, and myotube atrophy were inhibited by PPARβ/δ blocker or siRNA. Importantly, muscle wasting induced in rats by dexamethasone or sepsis was prevented by treatment with a PPARβ/δ inhibitor. The present results suggest that PPARβ/δ regulates FOXO1 activation in glucocorticoid- and sepsis-induced muscle wasting and that treatment with a PPARβ/δ inhibitor may ameliorate loss of muscle mass in these conditions. |
| first_indexed | 2024-12-20T02:15:38Z |
| format | Article |
| id | doaj.art-02178e2a45e6433ca35b5e12287a8793 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:15:38Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-02178e2a45e6433ca35b5e12287a87932022-12-21T19:56:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5972610.1371/journal.pone.0059726PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting.Estibaliz CastilleroNima AlamdariZaira AversaAniket GuravPer-Olof HasselgrenFOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1 expression in muscle wasting are poorly understood. We hypothesized that the transcription factor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) upregulates muscle FOXO1 expression and activity with a downstream upregulation of atrogin-1 and MuRF1 expression during sepsis and glucocorticoid treatment and that inhibition of PPARβ/δ activity can prevent muscle wasting. We found that activation of PPARβ/δ in cultured myotubes increased FOXO1 activity, atrogin-1 and MuRF1 expression, protein degradation and myotube atrophy. Treatment of myotubes with dexamethasone increased PPARβ/δ expression and activity. Dexamethasone-induced FOXO1 activation and atrogin-1 and MuRF1 expression, protein degradation, and myotube atrophy were inhibited by PPARβ/δ blocker or siRNA. Importantly, muscle wasting induced in rats by dexamethasone or sepsis was prevented by treatment with a PPARβ/δ inhibitor. The present results suggest that PPARβ/δ regulates FOXO1 activation in glucocorticoid- and sepsis-induced muscle wasting and that treatment with a PPARβ/δ inhibitor may ameliorate loss of muscle mass in these conditions.http://europepmc.org/articles/PMC3605288?pdf=render |
| spellingShingle | Estibaliz Castillero Nima Alamdari Zaira Aversa Aniket Gurav Per-Olof Hasselgren PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting. PLoS ONE |
| title | PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting. |
| title_full | PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting. |
| title_fullStr | PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting. |
| title_full_unstemmed | PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting. |
| title_short | PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting. |
| title_sort | pparβ δ regulates glucocorticoid and sepsis induced foxo1 activation and muscle wasting |
| url | http://europepmc.org/articles/PMC3605288?pdf=render |
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