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

Abstract

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.

Prenatal Amino Acid Supplementation to Improve Fetal Growth: A Systematic Review and Meta-Analysis

“…Most studies reporting on fetal growth after BCAA supplementation were performed in rats ( n = 7) [ 43 , 97 , 98 , 99 , 100 , 101 , 102 ], with a few in mice ( n = 1) [ 103 ] and pigs ( n = 2) [ 104 , 105 ]; no human studies were found ( Table A5 ). Leucine was the most investigated BCAA ( n = 9) [ 43 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 105 ], followed by valine ( n = 4) [ 43 , 97 , 98 , 104 ], and isoleucine ( n = 3) [ 43 , 98 , 99 ]. The studies performed by Brunner [ 43 ], Matsueda [ 97 ], and Mori [ 98 ] used all three BCAAs.…”

Leucine‐rich diet minimises liver glycogen mobilisation and modulates liver gluconeogenesis enzyme expression in tumour‐bearing cachectic rats

“…The Walker 256 tumour is widely used as an experimental model of cancer cachexia syndrome [19, 30–32]. Walker 256 carcinosarcoma cells (2.5 × 10 6 viable cells) were injected subcutaneously into the right flank of the experimental rats on the first day of the experiment.…”

Maternal Leucine-Rich Diet Minimises Muscle Mass Loss in Tumour-bearing Adult Rat Offspring by Improving the Balance of Muscle Protein Synthesis and Degradation

“…In an experimental model of cancer cachexia, a 3% leucine-rich diet showed positive effects on protein synthesis in skeletal muscle, leading activation of the mTOR pathway and reduction of protein degradation by inhibiting the ubiquitin-proteasome pathway in Walker-256 tumour-bearing rats [12,13,14]. Studies also showed attenuated degradation and modulation of both lysosomal and calcium-dependent proteolysis in animals fed this diet [15,16]. Considering the leucine supplementation capacity to cross de placental barrier and the ability to modify the breast milk composition [17,18,19], there is some evidence supporting the use of a maternal diet as a preventive approach.…”