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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...
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/PMC3605288/ https://www.ncbi.nlm.nih.gov/pubmed/23555761 http://dx.doi.org/10.1371/journal.pone.0059726 |
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author | Castillero, Estibaliz Alamdari, Nima Aversa, Zaira Gurav, Aniket Hasselgren, Per-Olof |
author_facet | Castillero, Estibaliz Alamdari, Nima Aversa, Zaira Gurav, Aniket Hasselgren, Per-Olof |
author_sort | Castillero, Estibaliz |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3605288 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36052882013-04-03 PPARβ/δ Regulates Glucocorticoid- and Sepsis-Induced FOXO1 Activation and Muscle Wasting Castillero, Estibaliz Alamdari, Nima Aversa, Zaira Gurav, Aniket Hasselgren, Per-Olof PLoS One Research Article 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. Public Library of Science 2013-03-21 /pmc/articles/PMC3605288/ /pubmed/23555761 http://dx.doi.org/10.1371/journal.pone.0059726 Text en © 2013 Castillero 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 Castillero, Estibaliz Alamdari, Nima Aversa, Zaira Gurav, Aniket Hasselgren, Per-Olof PPARβ/δ Regulates Glucocorticoid- and Sepsis-Induced FOXO1 Activation and Muscle Wasting |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605288/ https://www.ncbi.nlm.nih.gov/pubmed/23555761 http://dx.doi.org/10.1371/journal.pone.0059726 |
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