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

Abstract

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.

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

“…We evaluated the influence of the maternal diet on adulthood because the parameters evaluated for the dam and the weight increase in the offspring showed that the maternal diet did not affect these morphometric parameters. Additionally, the maternal leucine-rich diet did not affect tumour size, which is in accordance with previous studies [12,20], but it minimised the cancer cachexia-induced damage to the skeletal muscle, in this case the gastrocnemius tissue.…”

“…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. Our previous study showed that 3% leucine administered as a maternal supplement could modulate cancer cachexia-induced liver damages in tumour-bearing adult offspring [20].…”

Walker-256 Tumour-Induced Cachexia Altered Liver Metabolomic Profile and Function in Weanling and Adult Rats

“…Following literature data, here, we found a diminished carcass weight added to a reduction in serum albumin and total protein levels, features related to the cachexia process. These results were similar to previous studies using the same experimental model [26][27][28]. Of note, these alterations happened in both tumour-bearing groups but were more severe in WW animals, likely suggesting a higher spoliation in younger hosts, corroborating our previous report [17].…”

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

“…The control diet (C) contained 18% protein, of which 1.6% L-leucine, and the leucine-rich diet (L) had the same quantity of protein (18%) with the addition of 3% L-leucine (4.6% L-leucine in total). The amount of L-leucine was based on our previous experimental study [ 22 ].…”