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 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.
Highlights
Cancer cachexia is a multi-factorial syndrome associated with skeletal muscle wasting with or without adipose tissue loss, chronic systemic inflammation, anorexia, poor prognosis, and reduced survival [1]
Several metabolomic studies into cancer cachexia were based on metabolomic analysis of the serum, giving a global view of the metabolic alterations induced by this syndrome in the host [15,16,17,18,19]
Analysis of the skeletal muscle metabolites could provide a direct clue for biomarker research and be applied for early detection of this syndrome [20]
Summary
Cancer cachexia is a multi-factorial syndrome associated with skeletal muscle wasting with or without adipose tissue loss, chronic systemic inflammation, anorexia, poor prognosis, and reduced survival [1]. Cachexia is considered to be a multi-organ syndrome, since it leads to multiple organ metabolism changes such as in the heart, liver, brain, white and brown adipose tissue, and especially skeletal muscle tissue, the most affected one [4]. Fearon and colleagues have described that cachexia has three stages: precachexia, cachexia, and refractory cachexia [5]. The progression of this syndrome is related to multiple factors, including systemic inflammation, cancer stage, anorexia, and response to anti-cancer treatment. It is critically important to identify the onset of cachexia earlier and develop molecular interventions to reduce or delay the progression of this disease [7]
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