A Time-Course Comparison of Skeletal Muscle Metabolomic Alterations in Walker-256 Tumour-Bearing Rats at Different Stages of Life

• Published in: Metabolites Vol. 11; no. 6; p. 404
• Main Authors: Chiocchetti, Gabriela de Matuoka e, Lopes-Aguiar, Leisa, Miyaguti, Natália Angelo da Silva, Viana, Lais Rosa, Salgado, Carla de Moraes, Orvoën, Ophelie Ocean, Florindo, Derly, Santos, Rogério Williams dos, Cintra Gomes-Marcondes, Maria Cristina
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20.06.2021; MDPI
• Subjects: Age; Amino acids; Animals; Anorexia; Biosynthesis; Cachexia; Cancer; Evolution; Gastrocnemius muscle; Lipids; Medical prognosis; Metabolism; Metabolites; Metabolomics; Musculoskeletal system; Nitrogen; NMR; Nuclear magnetic resonance; Skeletal muscle; time-course; Tumors; Walker-256 tumour; Weight control; Young adults
• ISSN: 2218-1989; 2218-1989
• DOI: 10.3390/metabo11060404

Cancer cachexia is a severe wasting condition that needs further study to find ways to minimise the effects of damage and poor prognosis. Skeletal muscle is the most impacted tissue in cancer cachexia; thus, elucidation of its metabolic alterations could provide a direct clue for biomarker research and be applied to detect this syndrome earlier. In addition, concerning the significant changes in the host metabolism across life, this study aimed to compare the metabolic muscle changes in cachectic tumour-bearing hosts at different ages. We performed 1H-NMR metabolomics in the gastrocnemius muscle in weanling and young adult Walker-256 tumour-bearing rats at different stages of tumour evolution (initial, intermediate, and advanced). Among the 49 metabolites identified, 24 were significantly affected throughout tumour evolution and 21 were significantly affected regarding animal age. The altered metabolites were mainly related to increased amino acid levels and changed energetic metabolism in the skeletal muscle, suggesting an expressive catabolic process and diverted energy production, especially in advanced tumour stages in both groups. Moreover, these changes were more severe in weanling hosts throughout tumour evolution, suggesting the distinct impact of cancer cachexia regarding the host’s age, highlighting the need to adopting the right animal age when studying cancer cachexia.