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.

Leucine-rich Diet Improved Muscle Function in Cachectic Walker 256 Tumor-bearing Wistar Rats

2021 ◽  
Author(s):  
Laís Viana ◽  
Gabriela Chiocchetti ◽  
Lucas Oroy ◽  
Willians Vieira ◽  
Carla Salgado ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Muscle Atrophy ◽  
Muscle Function ◽  
Cancer Cachexia ◽  
Muscle Protein ◽  
Tumor Bearing ◽  
Muscle Protein Degradation ◽  
Walker 256 ◽  
Walker 256 Tumor

Abstract Background: Skeletal muscle atrophy occurs in several pathological conditions such as cancer, a condition termed cancer cachexia. This condition is associated with an increase in morbidity and poor treatment response, decreasing quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy preventing muscle atrophy in cancer cachexia hosts. Besides muscle atrophy, muscle function loss is even more important to the patient’s quality of life. Therefore, this study aimed to evaluate the effects of leucine-rich diet on muscle function activity of cachectic Walker 256 tumor-bearing rats and to correlate such effects with molecular pathways of muscle atrophy. Methods: Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet: Control (C) and Walker 256 tumor-bearing (W), and two other groups were fed with a leucine-rich diet: Leucine Control (L) and Leucine Walker 256 tumor-bearing (LW). The functional analysis (walking, behavior, and strength tests) was measured and before and after tumor 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 performed. Results: Walker 256 tumor growth led to muscle function decline, cachexia manifestation symptoms, muscle fiber cross-section area reduction, associated with the altered morphological pattern and classical muscle protein degradation pathway activation, with up-regulation of FoXO1, MuRF1, and 20S proteins. On the other hand, a leucine-rich diet improved muscle strength while reducing the decline of walking and behavior, partially improving the cachexia manifestations and preventing muscle atrophy and protein degradation in Walker 256 tumor-bearing rats. Conclusions: A leucine-rich diet diminished muscle protein degradation and enhanced oxidative pathways, leading to better muscle functional performance.

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.

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 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.

Beta-hydroxy beta-methyl butyrate decreases muscle protein degradation via increased Akt/FoxO3a signaling and mitochondrial biogenesis in weanling piglets after lipopolysaccharide challenge

2019 ◽  
Vol 10 (8) ◽  
pp. 5152-5165 ◽  
Author(s):  
Yehui Duan ◽  
Changbing Zheng ◽  
Yinzhao Zhong ◽  
Bo Song ◽  
Zhaoming Yan ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Muscle Atrophy ◽  
Mitochondrial Biogenesis ◽  
Muscle Protein ◽  
Methyl Butyrate ◽  
Weanling Piglets ◽  
Muscle Protein Degradation ◽  
Lipopolysaccharide Challenge

The aim of this study was to investigate the effects of dietary β-hydroxy-β-methylbutyrate (HMB) on lipopolysaccharide (LPS)-induced muscle atrophy and to investigate the mechanisms involved.

scholarly journals α‐Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway

2017 ◽  
Vol 32 (1) ◽  
pp. 488-499 ◽  
Author(s):  
Xingcai Cai ◽  
Yexian Yuan ◽  
Zhengrui Liao ◽  
Kongping Xing ◽  
Canjun Zhu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Degradation ◽  
Muscle Atrophy ◽  
Muscle Protein ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Degradation

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 Cancer Takes a Toll on Skeletal Muscle by Releasing Heat Shock Proteins—An Emerging Mechanism of Cancer-Induced Cachexia

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1272 ◽  
Author(s):  
Thomas K Sin ◽  
Guohua Zhang ◽  
Zicheng Zhang ◽  
Song Gao ◽  
Min Li ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Degradation ◽  
Cancer Cachexia ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Downstream Signaling ◽  
Muscle Protein Degradation ◽  
Shock Proteins ◽  
And Function

Cancer-associated cachexia (cancer cachexia) is a major contributor to the modality and mortality of a wide variety of solid tumors. It is estimated that cachexia inflicts approximately ~60% of all cancer patients and is the immediate cause of ~30% of all cancer-related death. However, there is no established treatment of this disorder due to the poor understanding of its underlying etiology. The key manifestations of cancer cachexia are systemic inflammation and progressive loss of skeletal muscle mass and function (muscle wasting). A number of inflammatory cytokines and members of the TGFβ superfamily that promote muscle protein degradation have been implicated as mediators of muscle wasting. However, clinical trials targeting some of the identified mediators have not yielded satisfactory results. Thus, the root cause of the muscle wasting associated with cancer cachexia remains to be identified. This review focuses on recent progress of laboratory studies in the understanding of the molecular mechanisms of cancer cachexia that centers on the role of systemic activation of Toll-like receptor 4 (TLR4) by cancer-released Hsp70 and Hsp90 in the development and progression of muscle wasting, and the downstream signaling pathways that activate muscle protein degradation through the ubiquitin–proteasome and the autophagy–lysosome pathways in response to TLR4 activation. Verification of these findings in humans could lead to etiology-based therapies of cancer cachexia by targeting multiple steps in this signaling cascade.

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