Supraphysiologic Administration of GDF11 Induces Cachexia in Part by Upregulating GDF15.
Cell Rep
; 22(6): 1522-1530, 2018 02 06.
Article
em En
| MEDLINE
| ID: mdl-29425507
ABSTRACT
The age-related effects of GDF11 have been a subject of controversy. Here, we find that elevated GDF11 causes signs of cachexia in mice reduced food intake, body weight, and muscle mass. GDF11 also elicited a significant elevation in plasma Activin A, previously shown to contribute to the loss of skeletal muscle. The effects of GDF11 on skeletal muscle could be reversed by administration of antibodies to the Activin type II receptors. In addition to the effects on muscle, GDF11 increased plasma GDF15, an anorectic agent. The anorexia, but not the muscle loss, could be reversed with a GDF15-neutralizing antibody. GDF15 upregulation is due to GDF11-induced recruitment of SMAD2/3 to the GDF15 promoter. Inhibition of GDF15 can restore appetite but cannot restore the GDF11-induced loss of muscle mass, which requires blockade of ActRII signaling. These findings are relevant for treatment of cachexia.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Caquexia
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Proteínas Morfogenéticas Ósseas
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Fator 15 de Diferenciação de Crescimento
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Fatores de Diferenciação de Crescimento
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article