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

Author(s)

de Matuoka e Chiocchetti, Gabriela ^[1] ; Lopes-Aguiar, Leisa ^[1] ; da Silva Miyaguti, Natalia Angelo ^[1] ; Viana, Lais Rosa ^[1] ; Salgado, Carla de Moraes ^[1] ; Orvoen, Ophelie Ocean ^{[1, 2]} ; Florindo, Derly ^[1] ; dos Santos, Rogerio Williams ^[1] ; Cintra Gomes-Marcondes, Maria Cristina ^[1]

Affiliation

^[1] Univ Estadual Campinas, Biol Inst, Dept Struct & Funct Biol, Lab Nutr & Canc, UNICAMP, Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil

^[2] Univ Angers, Biol Dept, F-49000 Anger - France

• Document type: Journal article
• Source: METABOLITES; v. 11, n. 6 JUN 2021.
• Web of Science Citations: 0

Abstract

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 H-1-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. (AU)

• FAPESP's process: 17/02739-4 - Nutrition and cancer: study of molecular, proteomic and metabolomic aspects of experimental model of cachexia
• Grantee: Maria Cristina Cintra Gomes Marcondes
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 15/21890-0 - Effect of leucine, ketogenic and combined diets in tumor growth, cachectic state and metabolomic systemic profile, muscle and tumor in rats with cancer cachexia (Walker 256 model)
• Grantee: Laís Rosa Viana
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 18/20637-7 - Evaluation of the effects of nutritional supplementation with leucine on the placental activity of Walker 256 tumour-bearing rats during pregnancy evolution
• Grantee: Carla de Moraes Salgado
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 19/14803-4 - Nutrition and Câncer. Molecular, Proteomic and Metabolomic aspects in experimental model of cachexia.
• Grantee: Gabriela de Matuoka e Chiocchetti
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 19/13937-7 - Nutrition and Câncer. Molecular, Proteomic and Metabolomic aspects in experimental model of cachexia.
• Grantee: Natália Miyaguti Angelo da Silva
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 19/20558-2 - Nutrition and Câncer. Molecular, Proteomic and Metabolomic aspects in experimental model of cachexia.
• Grantee: Leisa Lopes Aguiar
• Support type: Scholarships in Brazil - Post-Doctorate