Walker-256 Tumour-Induced Cachexia Altered Liver Metabolomic Profile and Function in Weanling and Adult Rats

Author(s)

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

Affiliation

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

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

• Document type: Journal article
• Source: METABOLITES; v. 11, n. 12 DEC 2021.
• Web of Science Citations: 0

Abstract

Cancer cachexia occurs in up to 85% of advanced cancer patients, affecting different tissues and organs, mainly the liver, which plays a central role in body metabolism control. However, liver responses to cancer cachexia progression are still poorly understood. Considering the possible different challenges provided by the rodent's phase of life and the cachexia progression, we evaluated the liver metabolic alterations affected by Walker-256 tumour growth in weanling and young-adult rats. For this, we applied a metabolomics approach associated with protein and gene expression analyses. Higher amino acid levels and impaired glucose metabolism were important features in tumour-bearing animals' liver tissue. The weanling hosts had more pronounced cachexia, with higher carcass spoliation, liver lipid metabolism and impaired CII and CIV mitochondrial complexes. The liver alterations in young adult tumour-bearing rats were related to energy status and nucleotide metabolites, such as uridine, NAD+, xanthosine, hypoxanthine and inosine. In conclusion, the Walker-256 tumour-induced cachexia impaired liver metabolism, being more severe in the weanling hosts. Further studies are needed to correlate these changes in the preclinical model, which can be correlated to the clinical features of cancer cachexia, allowing for a translational potential involving the liver function and its responses to potential treatments. (AU)

• 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 Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/20558-2 - Nutrition and Câncer. Molecular, Proteomic and Metabolomic aspects in experimental model of cachexia.
• Grantee: Leisa Lopes Aguiar
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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 Opportunities: Scholarships in Brazil - Post-Doctoral
• 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 Opportunities: Scholarships in Brazil - Post-Doctoral
• 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 Opportunities: Research Projects - Thematic Grants
• 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 Opportunities: Scholarships in Brazil - Master