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.
Highlights
Introduction1. Introduction with regard to jurisdictional claims in Cancer cachexia is marked by a disrupted metabolism, mainly affecting the skeletal muscle, accompanied or not by a loss of body fat mass, which occurs in up to 85% of advanced cancer patients, being responsible for at least 22% of cancer-related deaths [1,2]
Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas 13083862, SP, Brazil; Biology Department, Université d’Angers, 4900 Angers, France
After the tumour growth, we observed a negative impact in host weight, as both tumour-bearing groups had a significant decrease in carcass weight (WW < WC, ≈31% of reduction; AW < AC, ≈13% of reduction; where tumour and age factors were significant; Table S1)
Summary
1. Introduction with regard to jurisdictional claims in Cancer cachexia is marked by a disrupted metabolism, mainly affecting the skeletal muscle, accompanied or not by a loss of body fat mass, which occurs in up to 85% of advanced cancer patients, being responsible for at least 22% of cancer-related deaths [1,2]. Introduction with regard to jurisdictional claims in Cancer cachexia is marked by a disrupted metabolism, mainly affecting the skeletal muscle, accompanied or not by a loss of body fat mass, which occurs in up to 85% of advanced cancer patients, being responsible for at least 22% of cancer-related deaths [1,2] It is considered a multiorgan syndrome, affecting other organs and tissues, including damaging the hepatic system [1].
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