Light aerobic physical exercise in combination with leucine and/or glutamine-rich diet can improve the body composition and muscle protein metabolism in young tumor-bearing rats

Salomão, Emilianne Miguel; Marcondes, Maria Cristina Cintra Gomes

doi:10.1007/s13105-012-0164-0

Cited by 25 publications

(32 citation statements)

References 36 publications

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“…Our previous work showed some important impairments in skeletal muscle in tumour‐bearing rats, which had increased chymotrypsin activity, representing enhancements of the ubiquitin–proteasome pathway . The present results likely suggest that the higher proteolytic activity (increased chymotrypsin activity) that is associated with higher cell activity (higher AP activity) in heart tissue could be responsible for the ECG failure that was observed only in group W. In our previous research, as also found here, the leucine‐rich diet also minimized the observed changes in those enzymes, even in the heart. Despite the presence of tumour, the LW group exhibited some improvements in cardiac tissue, with minimal damaging effects produced by tumour development, as confirmed by the significant diet interaction effect.…”

Section: Discussionsupporting

confidence: 82%

Nutritional leucine supplementation attenuates cardiac failure in tumour‐bearing cachectic animals

Toneto

Ramos

Salomão

et al. 2016

J cachexia sarcopenia muscle

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BackgroundThe condition known as cachexia presents in most patients with malignant tumours, leading to a poor quality of life and premature death. Although the cancer‐cachexia state primarily affects skeletal muscle, possible damage in the cardiac muscle remains to be better characterized and elucidated. Leucine, which is a branched chain amino acid, is very useful for preserving lean body mass. Thus, this amino acid has been studied as a coadjuvant therapy in cachectic cancer patients, but whether this treatment attenuates the effects of cachexia and improves cardiac function remains poorly understood. Therefore, using an experimental cancer‐cachexia model, we evaluated whether leucine supplementation ameliorates cachexia in the heart.MethodsMale Wistar rats were fed either a leucine‐rich or a normoprotein diet and implanted or not with subcutaneous Walker‐256 carcinoma. During the cachectic stage (approximately 21 days after tumour implantation), when the tumour mass was greater than 10% of body weight, the rats were subjected to an electrocardiogram analysis to evaluate the heart rate, QT‐c, and T wave amplitude. The myocardial tissues were assayed for proteolytic enzymes (chymotrypsin, alkaline phosphatase, cathepsin, and calpain), cardiomyopathy biomarkers (myeloperoxidase, tissue inhibitor of metalloproteinases, and total plasminogen activator inhibitor 1), and caspase‐8, ‐9, ‐3, and ‐7 activity.ResultsBoth groups of tumour‐bearing rats, especially the untreated group, had electrocardiography alterations that were suggestive of ischemia, dilated cardiomyopathy, and sudden death risk. Additionally, the rats in the untreated tumour‐bearing group but not their leucine‐supplemented littermates exhibited remarkable increases in chymotrypsin activity and all three heart failure biomarkers analysed, including an increase in caspase‐3 and ‐7 activity.ConclusionsOur data suggest that a leucine‐rich diet could modulate heart damage, cardiomyocyte proteolysis, and apoptosis driven by cancer‐cachexia. Further studies must be conducted to elucidate leucine's mechanisms of action, which potentially includes the modulation of the heart's inflammatory process.

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Section: Discussionsupporting

confidence: 82%

Nutritional leucine supplementation attenuates cardiac failure in tumour‐bearing cachectic animals

Toneto

Ramos

Salomão

et al. 2016

J cachexia sarcopenia muscle

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“…In our previous data, the tyrosine content was inversely proportional to the tyrosine release, indicating protein degradation [23,27,32]. Conversely, all of the leucine groups had decreased tyrosine contents when compared to the control group, although no difference was found among the leucine groups (Table 1).…”

Section: Mac16 Tumor Growth and Leucine Supplementation Increase Pc5 mentioning

confidence: 67%

“…The normoprotein control diet consisted of 18% protein (casein was the sole source of protein, which contained 1.6% Lleucine). The leucine-rich diet contained 18% protein and an additional 3% Lleucine [32] (for humans, this dosage corresponds to an intake of ;2 g leucine per day). Both diets contained similar amounts of nitrogen (;13.2 mg N 2 /100 g diet).…”

Section: Animalsmentioning

confidence: 99%

“…The amino acids in the leucine-rich diet were adjusted to reduce the equivalent amount of carbohydrates required to maintain isocaloric diets; the other ingredients-fat, fiber, salt, and vitamin mix as well as cystine and choline-were the same as in the normoprotein diet. The composition of these diets has been previously published [31][32][33]. The Lleucine and cornstarch were kindly provided by Ajinomoto Brasil and Corn Products, respectively.…”

Section: Animalsmentioning

confidence: 99%

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A Leucine-Rich Diet Modulates the Tumor-Induced Down-Regulation of the MAPK/ERK and PI3K/Akt/mTOR Signaling Pathways and Maintains the Expression of the Ubiquitin-Proteasome Pathway in the Placental Tissue of NMRI Mice1

Viana

Marcondes

2015

Biology of Reproduction

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Placental tissue injury is concomitant with tumor development. We investigated tumor-driven placental damage by tracing certain steps of the protein synthesis and degradation pathways under leucine-rich diet supplementation in MAC16 tumor-bearing mice. Cell signaling and ubiquitin-proteasome pathways were assessed in the placental tissues of pregnant mice, which were distributed into three groups on a control diet (pregnant control, tumor-bearing pregnant, and pregnant injected with MAC-ascitic fluid) and three other groups on a leucine-rich diet (pregnant, tumor-bearing pregnant, and pregnant injected with MAC-ascitic fluid). MAC tumor growth down-regulated the cell-signaling pathways of the placental tissue and decreased the levels of IRS-1, Akt/PKB, Erk/MAPK, mTOR, p70S6K, STAT3, and STAT6 phosphorylated proteins, as assessed by the multiplex Millipore Luminex assay. Leucine supplementation maintained the levels of these proteins within the established cell-signaling pathways. In the tumor-bearing group (MAC) only, the placental tissue showed increased PC5 mRNA expression, as assessed by quantitative RT-PCR, decreased 19S and 20S protein expression, as assessed by Western blot analysis, and decreased placental tyrosine levels, likely reflecting up-regulation of the ubiquitin-proteasome pathway. Similar effects were found in the pregnant injected with MAC-ascitic fluid group, confirming that the effects of the tumor were mimicked by MAC-ascitic fluid injection. Although tumor progression occurred, the degradation pathway-related protein levels were modulated under leucine-supplementation conditions. In conclusion, tumor evolution reduced the protein expression of the cell-signaling pathway associated with elevated protein degradation, thereby jeopardizing placental activity. Under the leucine-rich diet, the impact of cancer on placental function could be minimized by improving the cell-signaling activity and reducing the proteolytic process.

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“…The diets were supplemented with a mixture of vitamins, minerals, cysteine and choline. The control diet contained 1.6% L-leucine, and the leucine-rich diet contained 4.6% L-leucine; these diets were identical to those used in our previous experimental studies [5,24-26]. …”

Section: Methodsmentioning

confidence: 99%

Leucine-rich diet supplementation modulates foetal muscle protein metabolism impaired by Walker-256 tumour

Cruz

Marcondes

2014

Reprod Biol Endocrinol

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BackgroundCancer-cachexia induces a variety of metabolic disorders of protein turnover and is more pronounced when associated with pregnancy. Tumour-bearing pregnant rats have impaired protein balance, which decreases protein synthesis and increases muscle breakdown. Because branched-chain amino acids, especially leucine, stimulate protein synthesis, we investigated the effect of a leucine-rich diet on protein metabolism in the foetal gastrocnemius muscles of tumour-bearing pregnant rats.MethodsFoetuses of pregnant rats with or without Walker 256 tumours were divided into six groups. During the 20 days of the experiment, the pregnant groups were fed with either a control diet (C, control rats; W, tumour-bearing rats; Cp, rats pair-fed the same normoprotein-diet as the W group) or with a leucine-rich diet (L, leucine rats; LW, leucine tumour-bearing rats; and Lp, rats pair-fed the same leucine-rich diet as the LW group). After the mothers were sacrificed, the foetal gastrocnemius muscle samples were resected, and the protein synthesis and degradation and tissue chymotrypsin-like, cathepsin and calpain enzyme activities were assayed. The muscle oxidative enzymes (catalase, glutathione-S-transferase and superoxide dismutase), alkaline phosphatase enzyme activities and lipid peroxidation (malondialdehyde) were also measured.ResultsTumour growth led to a reduction in foetal weight associated with decreased serum protein, albumin and glucose levels and low haematocrit in the foetuses of the W group, whereas in the LW foetuses, these changes were less pronounced. Muscle protein synthesis (measured by L-[3H]-phenylalanine incorporation) was reduced in the W foetuses but was restored in the LW group. Protein breakdown (as assessed by tyrosine release) was enhanced in the L and W groups, but chymotrypsin-like activity increased only in group W and tended toward an increase in the LW foetuses. The activity of cathepsin H was significantly higher in the W group foetuses, but the proteolytic calcium-dependent pathway showed similar enzyme activity. In parallel, an intense oxidative stress process was observed only in the group W foetuses.ConclusionsThese data suggested that the proteasomal and lysosomal proteolytic pathways and oxidative stress are likely to participate in the process of foetal muscle catabolism of Walker’s tumour-bearing pregnant rats. The present work shows that foetal muscle can be protected by supplementation with a leucine-rich diet.

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Light aerobic physical exercise in combination with leucine and/or glutamine-rich diet can improve the body composition and muscle protein metabolism in young tumor-bearing rats

Cited by 25 publications

References 36 publications

Nutritional leucine supplementation attenuates cardiac failure in tumour‐bearing cachectic animals

Nutritional leucine supplementation attenuates cardiac failure in tumour‐bearing cachectic animals

A Leucine-Rich Diet Modulates the Tumor-Induced Down-Regulation of the MAPK/ERK and PI3K/Akt/mTOR Signaling Pathways and Maintains the Expression of the Ubiquitin-Proteasome Pathway in the Placental Tissue of NMRI Mice1

Leucine-rich diet supplementation modulates foetal muscle protein metabolism impaired by Walker-256 tumour

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