Emilianne Miguel Salomão

Physical Exercise and a Leucine-Rich Diet Modulate the Muscle Protein Metabolism in Walker Tumor-Bearing Rats

Leucine-supplemented diet can recover lean body mass and preserve muscle protein mass. Additionally, physical exercise can be an excellent alternative to improve the rehabilitation of cancer patients. Knowing these facts, we examined the effects of a leucine-rich diet with or without physical aerobic exercise on muscle protein metabolism in Walker tumor-bearing rats. Young rats were divided into 4 groups that did or did not perform light aerobic exercise (swim training) and were on a leucine-rich diet or a control diet for 2 mo. After this time, these animals were implanted or not with tumors (subcutaneously) following groups for either control diet or leucine-rich diet fed rats: control, trained, tumor-bearing, and trained tumor-bearing. Twenty-one days after implantation, the tumor growth induced a decrease in the muscle protein synthesis and increased the catabolic process, which was associated with an increase in the expression of the ubiquitin-proteasome subunits (20S, 19S, and 11S). In contrast, the exercise program minimized the muscle degradation process and increased muscle myosin content. Additionally, leucine supplementation also modulated proteasome subunits, especially the 19S and 11S. In summary, the exercise has beneficial effects by reducing tumor growth, leading to an improvement in protein turnover especially when in conjunction with a leucine-rich diet.

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

The 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.

Leucine modulates the effect of Walker factor, a proteolysis-inducing factor-like protein from Walker tumours, on gene expression and cellular activity in C2C12 myotubes

Cancer-cachexia causes severe weight loss, particularly from the wasting of skeletal muscle, which occurs due to increased protein catabolism and/or decreased protein synthesis. The muscle protein degradation observed in cancer patients is mediated by a specific cytokine, proteolysis-inducing factor (PIF), which is produced by the tumour. This protein increases the ubiquitin-proteasome pathway activity, and the synthesis of muscle protein in these patients can be affected by several factors, including nutrient-related signalling. Some nutrients, such as leucine, can decrease the ubiquitin-proteasome pathway activity and increase the skeletal muscle protein content in cachectic animals. In this study, we investigated the effects of leucine on cell viability, morphology, functional proteasome activity, enzymatic activity, and protein synthesis and degradation in C2C12 myotubes exposed to the proteolysis-inducing factor (PIF)-like protein purified from Walker tumour-bearing rats. Walker factor (WF) had no cytotoxic effects on myotube cells and morphological characteristics were not altered in the presence of WF and/or leucine. However, increased alkaline phosphatase activity was observed. At higher WF concentrations, chymotrypsin-like activity, cathepsin B activity and 20S proteasome gene expression increased. Treating myotubes with leucine before exposure to WF causes leads to a decrease in proteasome activity as well as the activity of chymotrypsin and cathepsin enzymes. Total protein synthesis decreased in WF-treated cells concomitantly as protein degradation increased. After leucine exposure, the observed effects of WF were minimal or even reverted in some cases. Taken together, these results suggest an important modulatory effect for leucine on the effects of WF in C2C12 myotube cells.

Dietary leucine supplementation minimises tumour-induced damage in placental tissues of pregnant, tumour-bearing rats

BackgroundThe occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions. This association can exacerbate the conditions of both the mother and the foetus. The branched-chain amino acid leucine enhances cellular activity, particularly by increasing protein synthesis. This study aimed to analyse the modulatory effect of a leucine-rich diet on direct and indirect tumour-induced placental damage. This was accomplished by evaluating the expression of genes involved in protein synthesis and degradation and assessing anti-oxidant enzyme activity in placental tissues collected from pregnant, tumour-bearing rats.ResultsPregnant rats were either implanted with Walker 256 tumour cells or injected with ascitic fluid (to study the indirect effects of tumour growth) and then fed a leucine-rich diet. Animals in a control group underwent the same procedures but were fed a normal diet. On the 20th day of pregnancy, tumour growth was observed. Dams fed a normoprotein diet showed the greatest tumour growth. Injection with ascitic fluid mimicked the effects of tumour growth. Decreased placental protein synthesis and increased protein degradation were observed in both the tumour-bearing and the ascitic fluid-injected groups that were fed a normoprotein diet. These effects resulted in low placental DNA and protein content and high lipid peroxidation (measured by malondialdehyde content). Decreased placental protein synthesis-related gene expression was observed in the tumour group concomitant with increased expression of genes encoding protein degradation-associated proteins and proteolytic subunits.ConclusionsConsumption of a leucine-rich diet counteracted the effects produced by tumour growth and injection with ascitic fluid. The diet enhanced cell signalling, ameliorated deficiencies in DNA and protein content, and balanced protein synthesis and degradation processes in the placenta. The improvements in cell signalling included changes in the mTOR/eIF pathway. In conclusion, consumption of a leucine-rich diet improved placental metabolism and cell signalling in tumour-bearing rats, and these changes reduced the deleterious effects caused by tumour growth.

Leucine-Rich Diet and Light Aerobic Training Modulate GLUT4 Expression And Increase the Glycogen Content in the Gastrocnemius Muscle of Walker-256 Tumour-Bearing Rats

Leucine-Rich Diet and Light Aerobic Training Modulate GLUT4 Expression And Increase the Glycogen Content in the Gastrocnemius Muscle of Walker-256 Tumour-Bearing Rats The intense mobilisation of substrates during cancer induces the loss of body mass, which mainly results from the depletion of muscle protein due to increased proteolysis and/or decreased protein synthesis, leading to cachexia. Leucine is also used as an energy source and as a cell-signalling molecule by skeletal muscle. Additionally, physical activity increases glucose consumption, which reduces the levels of circulating glucose and insulin. This work investigated the effects of leucine supplementation and light aerobic-exercise (swimming) on muscle carbohydrate metabolism in Walker tumour-bearing rats. Trained adult rats were fed a leucine-rich diet and implanted with Walker-256 tumour cells. We assessed the levels of serum glucose, cytokine and hormone and muscle glycolytic gene expression, glycogen content and fibre size.

Combining Exercise with Glutamine Supplementation in Cancer-Cachexia Metabolism

Physical activity contributes to several beneficial processes including the management, treatment and prevention of various diseases, particularly cardiovascular and metabolic diseases. These well-being and health benefits include the improvement of the circulatory, respiratory and immune systems, reducing the diseases risks. Furthermore, in several studies, cancer prevention has been shown to be related to physical activity [1–3].

Prehydrolyzed dietary protein reduces gastrocnemial DNA without impairing physical capacity in the rat

Previous studies have shown that hydrolyzed proteins exhibit antioxidant properties and may confer physical and physiological advantages when consumed by the exercising rat. The purpose of this study was to compare the effects of feeding either intact (I) and partly hydrolyzed (H) milk whey proteins on gastrocnemial DNA contents and protein metabolism in exercising Wistar rats. Protein synthesis and degradation, protein and DNA contents, and concentration of the serum insulin-like growth factor -1 (IGF1) were determined in six experimental groups according to the type of protein consumed [casein (C), whey protein isolate (I), hydrolyzed whey protein (H) and level of physical activity (sedentary (S) and trained (T)]. H produced significantly lower rates of protein synthesis and degradation and DNA contents in the gastrocnemius, while no differences were observed in the total muscle protein content and serum levels of IGF1. These results indicate that consumption of prehydrolyzed whey protein alters muscle metabolism resulting in less DNA, but maintains the muscle protein levels constant and sustain or improves physical performance, compared to the unhydrolyzed protein. Keywords : Dietary protein, hydrolyzed whey protein, peptides in muscle metabolism, phenylalanine, tyrosine, physical activity African Journal of Biotechnology Vol. 12(16), pp. 2058-2064