PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice.
Appl Physiol Nutr Metab
; 47(9): 933-948, 2022 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-35700525
ABSTRACT
Cancer cachexia (CC) accounts for 20%-40% of cancer-related deaths. Mitochondrial aberrations have been shown to precede muscle atrophy in different atrophy models, including cancer. Therefore, this study investigated potential protection from the cachectic phenotype through overexpression of peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α). First, to establish potential of mitochondria-based approaches we showed that the mitochondrial antioxidant MitoTEMPO (MitoT) attenuates myotube atrophy induced by Lewis lung carcinoma (LLC) cell conditioned media. Next, cachexia was induced in muscle-specific PGC-1α overexpressing (MCK-PCG1α) or wildtype (WT) littermate mice by LLC implantation. MCK-PCG1α did not protect LLC-induced muscle mass loss. In plantaris, Atrogin mRNA content was 6.2-fold and â¼11-fold greater in WT-LLC vs WT-phosphate-buffered saline (PBS) for males and females, respectively (p < 0.05). MitoTimer redgreen ratio for male PGC was â¼65% higher than WT groups (p < 0.05), with â¼3-fold more red puncta in LLC than PBS (p < 0.05). Redgreen ratio was â¼56% lower in females WT-LLC vs PGC-LLC (p < 0.05). In females, no change in red puncta was noted across conditions. Lc3 mRNA content was â¼73% and 2-fold higher in male and female LLC mice, respectively, vs PBS (p < 0.05). While MitoT could mitigate cancer-induced atrophy in vitro, PGC-1α overexpression was insufficient to protect muscle mass and mitochondrial health in vivo despite mitigation of cachexia-associated signaling pathways.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Lewis
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
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Doenças Musculares
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Appl Physiol Nutr Metab
Assunto da revista:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
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MEDICINA ESPORTIVA
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METABOLISMO
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos