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 maternal leucine-rich diet showed a positive effect on the gastrocnemius muscle of adult tumor-bearing offspring. To improve the understanding of the metabolic alterations of cancer cachexia and correlate this to preventive treatment, we evaluated the ¹H NMR metabolic profiles from serum and gastrocnemius muscle samples of adult Wistar rats. These profiles were initially analyzed, and chemometrics tools were applied to investigate the following groups: C, control group; W, tumor-bearing group; L, the group without tumors and with a maternal leucine-rich diet; WL, the tumor-bearing group with a maternal leucine-rich diet. Tumor growth that led to a high protein breakdown in the W group was correlated to serum metabolites such as tyrosine, phenylalanine, histidine, glutamine, and tryptophan amino acids and uracil. Also, decreased muscle lactate, inversely to serum content, was found in the W group. Conversely, in the WL group, increased lactate in muscle and serum profiles was found, which could be correlated to the maternal diet effect. The muscle lipidomics and NAD⁺, NADP⁺, lysine, 4-aminohippurate, and glutamine metabolites pointed to modified energy metabolism and lower muscle mass loss in the WL group. In conclusion, this exploratory metabolomics analyses provided novel insights related to the Walker-256 tumor-bearing offspring metabolism modified by a maternal leucine-rich diet and the next steps in its investigation.

The anabolic effects of a supplemented diet with branched-chain amino acids, especially leucine, on skeletal muscle wasting and as a co-adjuvant in cancer treatment have been well-studied. Leucine is a precursor of protein synthesis and acts as a nutritional signal, affecting multiple metabolic processes (e.g., satiety, thermogenesis, energy efficiency, and body composition). Previous studies related to nutritional therapy have mainly focused on myopenia, which is the loss of skeletal muscle mass in some pathologies, including cancer. Leucine plays a role in the maintenance and even increase of lean body mass in healthy individuals as well as the prevention of disease states that culminate in myopenia. Herein, we review the available data addressing the mechanisms by which leucine acts as a cellular signal, thereby stimulating muscle protein synthesis, leading to the inhibition of muscle catabolism, especially in an experimental model of cancer cachexia. We also show differences found in the metabolomic and proteomic analyses, including the use of leucine in maternal diets as a preventative for muscle wasting as supported by our experimental data.

Scope: Nutritional supplementation of the maternal diet can modify the cancer susceptibility in adult offspring. Therefore, the authors evaluate the effects of a fish‐oil diet administered to a long‐term, during pre‐mating, gestation, and lactation, in reducing cancer‐cachexia damages in adult Walker‐256 tumor‐bearing offspring.Methods and Results: Female rats receive control or fish oil diet during pre‐mating, gestation, and lactation. After weaning, male offspring are fed the control diet until adulthood and distributed in (C) control adult‐offspring; (W) adult tumor‐bearing offspring; (OC) adult‐offspring of maternal fish oil diet; (WOC) adult tumor‐bearing offspring of maternal fish oil diet groups. Fat body mass is preserved, muscle expression of mechanistic target of rapamicin (mTOR) and eukariotic binding protein of eukariotic factor 4E (4E‐BP1) is modified, being associated with lower 20S proteasome protein expression, and the liver alanine aminotransferase (ALT) enzyme content maintained in the WOC group. Also, the OC group shows reduced triglyceridemia.Conclusion: In this experimental model of cachexia, the long‐term maternal supplementation is a positive strategy to improve liver function and lipid metabolism, as well as to modify muscle proteins expression in the mTOR pathway and also reduce the 20S muscle proteasome protein, without altering the tumor development and muscle wasting in adult tumor‐bearing offspring.