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

Abstract

Cachexia syndrome can affect cancer patients and new prevention strategies are required. Maternal nutritional supplementation can modify metabolic programming in the offspring, which lasts until adulthood. This could be a good approach against diseases such as cancer. A 3% leucine-rich diet treatment improved muscle protein turnover by modifying the mTOR and proteolytic pathways, thus we analysed whether maternal supplementation could ameliorate muscle protein turnover in adult offspring tumour-bearing rats. Pregnant Wistar rats received a control diet or 3% leucine-rich diet during pregnancy/lactation, and their weaned male offspring received a control diet until adulthood when they were distributed into following groups (n = 7–8 per group): C, Control; W, tumour-bearing; L, without tumour with a maternal leucine-rich diet; and WL, tumour-bearing with a maternal leucine-rich diet. Protein synthesis and degradation were assessed in the gastrocnemius muscle, focusing on the mTOR pathway, which was extensively altered in W group. However, the WL adult offspring showed no decrease in muscle weight, higher food intake, ameliorated muscle turnover, activated mTOR and p70S6K, and maintained muscle cathepsin H and calpain activities. Maternal leucine nutritional supplementation could be a positive strategy to improve muscle protein balance in cancer cachexia-induced muscle damage in adult offspring rats.

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

“…Intense body weight loss is expected during cancer cachexia, as verified in the AW animals in this study, and similar to others’ results for this same tumour model [ 27 , 28 , 29 ]. The tumour also affected the body growth and development in WW animals, but to a lesser extent, probably because this group was still in the growing phase.…”

Serum and Muscle 1H NMR-Based Metabolomics Profiles Reveal Metabolic Changes Influenced by a Maternal Leucine-Rich Diet in Tumor-Bearing Adult Offspring Rats

“…Therefore, strategies to prevent this condition are required. In this way, our previous study showed a maternal diet supplementation as a preventive approach against muscle wasting in an experimental model of cancer cachexia [3]. Based on leucine ability to cross the placental barrier and to modify the milk composition leading to epigenetics marks on the offspring [4][5][6], our study demonstrated that a leucine-rich diet when maternally administered diminished the muscle mass loss in adult offspring tumor-bearing rats.…”

“…Based on leucine ability to cross the placental barrier and to modify the milk composition leading to epigenetics marks on the offspring [4][5][6], our study demonstrated that a leucine-rich diet when maternally administered diminished the muscle mass loss in adult offspring tumor-bearing rats. This approach reduced the cachexia negative protein balance, which ameliorated the gastrocnemius muscle protein synthesis and decreased protein degradation, by activating the mechanistic target of rapamycin (mTOR) pathway and maintaining muscle cathepsin H and calpain activities [3].…”

Fish Oil Diet during Pre‐mating, Gestation, and Lactation in Adult Offspring Rats on Cancer Cachexia Prevention

“…Thus, other protein degradation pathways could be driving this spoliation, as seen in previous studies with the same tumor model. [39,40] Moreover, it would be interesting to evaluate the proteasomal activity correlating with the proteasomal protein expression levels. This analysis could also be important to clarify the maternal influence over this degradation pathway, which is a limitation of our study.…”