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

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 831
Author(s):  
Natália Angelo da Silva Miyaguti ◽  
Gabriela de Matuoka e Chiocchetti ◽  
Carla de Moraes Salgado ◽  
Leisa Lopes-Aguiar ◽  
Lais Rosa Viana ◽  
...  
Keyword(s):  
Young Adult ◽  
Cancer Cachexia ◽  
Liver Lipid ◽  
Preclinical Model ◽  
Energy Status ◽  
Advanced Cancer Patients ◽  
Adult Rats ◽  
Tumour Bearing ◽  
Walker 256 Tumour ◽  
Walker 256

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.

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

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 404
Author(s):  
Gabriela de Matuoka e Chiocchetti ◽  
Leisa Lopes-Aguiar ◽  
Natália Angelo da Silva Miyaguti ◽  
Lais Rosa Viana ◽  
Carla de Moraes Salgado ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Time Course ◽  
Cancer Cachexia ◽  
Tumour Bearing ◽  
Walker 256 Tumour ◽  
Walker 256 ◽  
Muscle Changes ◽  
The Right ◽  
Biomarker Research ◽  
Host Metabolism

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.

scholarly journals Leucine-Rich Diet Improved Muscle Function in Cachectic Walker 256 Tumour-Bearing Wistar Rats

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3272
Author(s):  
Laís Rosa Viana ◽  
Gabriela de Matuoka e Chiocchetti ◽  
Lucas Oroy ◽  
Willians Fernando Vieira ◽  
Estela Natacha Brandt Busanello ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Muscle Atrophy ◽  
Muscle Function ◽  
Cancer Cachexia ◽  
Muscle Protein ◽  
Tumour Bearing ◽  
Walker 256 Tumour ◽  
Muscle Protein Degradation ◽  
Walker 256

Skeletal muscle atrophy occurs in several pathological conditions, such as cancer, especially during cancer-induced cachexia. This condition is associated with increased morbidity and poor treatment response, decreased quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy to prevent muscle atrophy in patients suffering from cancer cachexia. Besides muscle atrophy, muscle function loss is even more important to patient quality of life. Therefore, this study aimed to investigate the potential beneficial effects of leucine supplementation on whole-body functional/movement properties, as well as some markers of muscle breakdown and inflammatory status. Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet (18% protein): Control (C) and Walker 256 tumour-bearing (W), and two other groups were fed with a leucine-rich diet (18% protein + 3% leucine): Leucine Control (L) and Leucine Walker 256 tumour-bearing (LW). A functional analysis (walking, behaviour, and strength tests) was performed before and after tumour inoculation. Cachexia parameters such as body weight loss, muscle and fat mass, pro-inflammatory cytokine profile, and molecular and morphological aspects of skeletal muscle were also determined. As expected, Walker 256 tumour growth led to muscle function decline, cachexia manifestation symptoms, muscle fibre cross-section area reduction, and classical muscle protein degradation pathway activation, with upregulation of FoxO1, MuRF-1, and 20S proteins. On the other hand, despite having no effect on the walking test, inflammation status or muscle oxidative capacity, the leucine-rich diet improved muscle strength and behaviour performance, maintained body weight, fat and muscle mass and decreased some protein degradation markers in Walker 256 tumour-bearing rats. Indeed, a leucine-rich diet alone could not completely revert cachexia but could potentially diminish muscle protein degradation, leading to better muscle functional performance in cancer cachexia.

scholarly journals Studies on the lipid metabolism of Walker 256 tumour-bearing rats during the development of cancer cachexia

IUBMB Life ◽  
1996 ◽  
Vol 39 (5) ◽  
pp. 1037-1047 ◽  
Author(s):  
M. C. L. Seelaender ◽  
C.M. Oller Do Nascimento ◽  
R. Curi ◽  
J. F. Williams
Keyword(s):  
Lipid Metabolism ◽  
Cancer Cachexia ◽  
Tumour Bearing ◽  
Walker 256 Tumour ◽  
Walker 256

scholarly journals Moderate exercise training since adolescence reduces Walker 256 tumour growth in adult rats

2019 ◽  
Vol 597 (15) ◽  
pp. 3905-3925 ◽  
Author(s):  
Veridiana Mota Moreira ◽  
Douglas Almeida ◽  
Claudinéia Conationi da Silva Franco ◽  
Rodrigo Mello Gomes ◽  
Kesia Palma‐Rigo ◽  
...  
Keyword(s):  
Exercise Training ◽  
Tumour Growth ◽  
Moderate Exercise ◽  
Adult Rats ◽  
Walker 256 Tumour ◽  
Walker 256 ◽  
Moderate Exercise Training

scholarly journals Leucine-Rich Diet Modulates the Metabolomic and Proteomic Profile of Skeletal Muscle during Cancer Cachexia

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1880 ◽  
Author(s):  
Bread Cruz ◽  
André Oliveira ◽  
Lais Rosa Viana ◽  
Leisa Lopes-Aguiar ◽  
Rafael Canevarolo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cancer Cachexia ◽  
Energy Generation ◽  
In Vitro Assays ◽  
Proteomic Profile ◽  
Adult Rats ◽  
Vitro Assay ◽  
Tumour Bearing

Background: Cancer-cachexia induces a variety of metabolic disorders, including skeletal muscle imbalance. Alternative therapy, as nutritional supplementation with leucine, shows a modulatory effect over tumour damage in vivo and in vitro. Method: Adult rats distributed into Control (C), Walker tumour-bearing (W), control fed a leucine-rich diet (L), and tumour-bearing fed a leucine-rich diet (WL) groups had the gastrocnemius muscle metabolomic and proteomic assays performed in parallel to in vitro assays. Results: W group presented an affected muscle metabolomic and proteomic profile mainly related to energy generation and carbohydrates catabolic processes, but leucine-supplemented group (WL) recovered the energy production. In vitro assay showed that cell proliferation, mitochondria number and oxygen consumption were higher under leucine effect than the tumour influence. Muscle proteomics results showed that the main affected cell component was mitochondria, leading to an impacted energy generation, including impairment in proteins of the tricarboxylic cycle and carbohydrates catabolic processes, which were modulated and improved by leucine treatment. Conclusion: In summary, we showed a beneficial effect of leucine upon mitochondria, providing information about the muscle glycolytic pathways used by this amino acid, where it can be associated with the preservation of morphometric parameters and consequent protection against the effects of cachexia.

Effects of lixisenatide treatment on mild cachexia and related metabolic abnormalities in Walker‐256 tumour‐bearing rats

2020 ◽  
Author(s):  
Débora L. Quintilhano ◽  
Daniele R. Miksza ◽  
Giuliana R. Biazi ◽  
Isabele G. Frasson‐Uemura ◽  
Maria Fernanda R. Graciano ◽  
...  
Keyword(s):  
Metabolic Abnormalities ◽  
Tumour Bearing ◽  
Walker 256 Tumour ◽  
Walker 256

The effect of melatonin chronic treatment upon macrophage and lymphocyte metabolism and function in Walker-256 tumour-bearing rats

1998 ◽  
Vol 82 (1) ◽  
pp. 81-89 ◽  
Author(s):  
E Martins Jr ◽  
L.C Fernandes ◽  
I Bartol ◽  
J Cipolla-Neto ◽  
L.F.B.P Costa Rosa
Keyword(s):  
Chronic Treatment ◽  
Tumour Bearing ◽  
Walker 256 Tumour ◽  
Walker 256 ◽  
And Function

scholarly journals 1H-NMR Based Serum Metabolomics Identifies Different Profile between Sarcopenia and Cancer Cachexia in Ageing Walker 256 Tumour-Bearing Rats

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 161
Author(s):  
Laís Rosa Viana ◽  
Leisa Lopes-Aguiar ◽  
Rafaela Rossi Rosolen ◽  
Rogerio Willians dos Santos ◽  
Maria Cristina Cintra Gomes-Marcondes
Keyword(s):  
1H Nmr ◽  
Muscle Protein ◽  
Life Quality ◽  
Tumour Bearing ◽  
Walker 256 Tumour ◽  
Muscle Catabolism ◽  
Muscle Protein Degradation ◽  
Walker 256 ◽  
Serum Metabolomics

Sarcopenia among the older population has been growing over the last few years. In addition, the incidence of cancers increases with age and, consequently, the development of cachexia related cancer. Therefore, the elucidation of the metabolic derangements of sarcopenia and cachexia are important to improve the survival and life quality of cancer patients. We performed the 1H-NMR based serum metabolomics in adult (A) and ageing (S) Walker 256 tumour-bearing rats in different stages of tumour evolution, namely intermediated (Wi) and advanced (Wa). Among 52 serum metabolites that were identified, 21 were significantly increased in S and 14 and 19 decreased in the Wi and Wa groups, respectively. The most impacted pathways by this metabolic alteration were related by amino acid biosynthesis and metabolism, with an upregulation in S group and downregulation in Wi and Wa groups. Taken together, our results suggest that the increase in metabolic profile in ageing rats is associated with the higher muscle protein degradation that releases several metabolites, especially amino acids into the serum. On the other hand, we hypothesise that the majority of metabolites released by muscle catabolism are used by tumours to sustain rapid cell proliferation and tumorigenesis.

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