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.

Cachexia is a cancer-associated metabolic syndrome that causes muscle spoliation, which leads to a reduced life quality of cancer patients. Maternal nutritional supplementation with the branched-chain amino acid leucine has been studied as an attempt to minimise/prevent the muscle waste, as an epigenetic effect from pregnancy and weaning periods during the environment modulatory role. Metabolomic analysis is an important technique to evaluate the preventive effects of maternal nutritional supplementation in a cachexia process. Thus, the present study analysed the possible regulatory effects of this supplementation on muscle metabolic profile of the adult offspring rats bearing a Walker-256 tumour. The skeletal muscle (gastrocnemius) was processed by 1H-NMRI analysis to determine the metabolomic profiles. The tumour-bearing rats were spoiled and had an increased muscle energy expenditure. The maternal leucine supplementation improved the energy availability for muscle function and activity.

Cancer-cachexia is a multifactorial chronic disease associated with high inflammation and loss of muscular and adipose tissues and affects 30% of cancer patients. A maternal diet with leucine could alter the inflammatory state and regulate protein synthesis positively, modulating the effects of cachexia. Metabolomic analyses are an important technique to value the effects of cachexia because of the identification of altered metabolites in serum samples and consequently evaluate the impacted metabolic pathways in these patients. Thus, we analysed the regulatory effects of maternal nutritional supplementation with leucine over the serum metabolic profile (using the 1H-NMR analysis) of the adult offspring rats bearing the Walker 256 tumour.The cachexia leads to a characteristic metabolic profile related to an increase in the glycolytic pathway, which is likely modulated by maternal leucine-rich diet that altered the 1H-NMRI serum metabolomic profile, improving the oxidative pathway.

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