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

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.

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

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

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.

Maternal nutritional supplementation with fish oil and/or leucine improves hepatic function and antioxidant defenses, and minimizes cachexia indexes in Walker-256 tumor-bearing rats offspring.

In this study, we hypothesized that throughout the pregnancy/weaning period, nutritional supplementation with leucine (which improves protein synthesis) and/or fish oil (rich in omega-3, which modulates oxidative stress) can minimize/improve cachexia-induced damage in rat offspring. Thus, we investigated the maternal supplementation with these nutrients over the modulation of cachexia index and liver function in tumor-bearing rats offspring. Pregnant rats were fed control, leucine, omega-3, and leucine/omega-3 diets, which were given throughout the gestational and weaning periods. The male offspring were subjected to a control diet until adulthood (120 days) and then distributed into 5 groups (n=4-6 per group): C, Control; W, tumor-bearing; WL, tumor-bearing group with a maternal leucine-rich diet; WO, tumor-bearing group with a maternal omega-3 diet; and WLO, tumor-bearing group with a maternal leucine-rich and omega-3 diet. The W group had a higher cachexia index (31.83 ± 2.9%), but this parameter decreased in the WO (P=0.0380) and WLO groups (P=0.0187). In addition, the W group had a lower survival rate, and the WLO group exhibited a trend toward increased survival (P=0.0505). The hepatic function in maternal supplemented groups was preserved, while the W group exhibited an increased aspartate-aminotransferase/alanine-aminotransferase ratios (P=0.0152) and also enhanced liver oxidative stress, with higher alkaline phosphatase (P=0.0190) and superoxide dismutase (P=0.0190) activities, and trended toward to higher malondialdehyde content (P=0.0556). In contrast, the maternal-supplemented groups had similar liver enzymes and malondialdehyde contents. Thus, we concluded that supplementing the maternal diet modulated/improved liver antioxidant responses and ameliorated the cachexia state in tumor-bearing rat offspring.