RRC ID 75833
著者 Miyazaki M, Sawada A, Sawamura D, Yoshida S.
タイトル Decreased insulin-like growth factor-1 expression in response to mechanical loading is associated with skeletal muscle anabolic resistance in cancer cachexia.
ジャーナル Growth Horm IGF Res
Abstract OBJECTIVE:Cachexia is a systemic metabolic syndrome characterized by loss of body weight and skeletal muscle mass during chronic wasting diseases, such as cancer. Skeletal muscle in cancer cachexia is less responsive to anabolic factors including mechanical loading; however, the precise molecular mechanism is largely unknown. In this study, we examined the underlying mechanism of anabolic resistance in skeletal muscle in a cancer cachexia model.
METHODS:CD2F1 mice (male, 8 weeks old) were subcutaneously transplanted (1 × 106 cells per mouse) with a mouse colon cancer-derived cell line (C26) as a model of cancer cachexia. Mechanical overload of the plantaris muscle by synergist tenotomy was performed during the 2nd week and the plantaris muscle was sampled at the 4th week following C26 transplantation.
RESULTS:The hypertrophic response of skeletal muscle (increased skeletal muscle weight/protein synthesis efficiency and activation of mechanistic target of rapamycin complex 1 signaling) associated with mechanical overload was significantly suppressed during cancer cachexia. Screening of gene expression profile and pathway analysis using microarray revealed that blunted muscle protein synthesis was associated with cancer cachexia and was likely induced by downregulation of insulin-like growth factor-1 (IGF-1) and impaired activation of IGF-1-dependent signaling.
CONCLUSIONS:These observations indicate that cancer cachexia induces resistance to muscle protein synthesis, which may be a factor for inhibiting the anabolic adaptation of skeletal muscle to physical exercise in cancer patients.
巻・号 69-70
ページ 101536
公開日 2023-1-1
DOI 10.1016/j.ghir.2023.101536
PII S1096-6374(23)00014-X
PMID 37229943
MeSH Animals Cachexia / complications Cachexia / metabolism Colonic Neoplasms* / complications Colonic Neoplasms* / metabolism Insulin-Like Growth Factor I* / metabolism Male Mice Muscle Proteins / metabolism Muscle, Skeletal / metabolism
IF 1.618
リソース情報
ヒト・動物細胞 Colon-26(RCB2657)