Castillero, EstibalizAlamdari, NimaAversa, ZairaGurav, Aniket NHasselgren, Per-Olof2013-10-172013Castillero, Estibaliz, Nima Alamdari, Zaira Aversa, Aniket Gurav, and Per-Olof Hasselgren. 2013. Pparβ/δ regulates glucocorticoid- and sepsis-induced foxo1 activation and muscle wasting. PLoS ONE 8(3): e59726.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:11180408FOXO1 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.en-USBiologyBiochemistryProteinsGeneticsGene ExpressionModel OrganismsAnimal ModelsRatMolecular Cell BiologyMedicineAnatomy and PhysiologyMusculoskeletal SystemMuscleMuscle BiochemistryMuscle FunctionsCritical Care and Emergency MedicineSepsisDrugs and DevicesJournal Article2013-10-1710.1371/journal.pone.0059726