Dados do Resumo

Título

Impact of Nutritional Supplementation and Spontaneous Exercise on Muscle Metabolic Alterations in Aged Wistar Rats with Cancer-Associated Cachexia

Introdução

Cancer-associated cachexia syndrome is characterized by the loss of muscle mass and adipose tissue, occurring in 80% of patients with advanced cancer. When this syndrome is combined with preexisting sarcopenia and a sedentary lifestyle, patients experience a decreased quality of life, increased chemotherapy toxicity, and reduced chances of survival. However, the biomolecular mechanisms involving sarcopenia, cachexia, nutritional supplementation, and exercise in cancer are not fully understood yet.

Objetivo

Therefore, we aimed to evaluate how cachexia and sarcopenia impact the metabolite concentrations in the gastrocnemius muscle of Wistar-aged rats (~400 days), and how their muscle metabolomic profile is influenced by supplementation and physical exercise.

Métodos

The experiment design (CEUA 5843/2021; 6110/2022) was divided into two main groups: Sedentary (S): without exercise and Exercised (E): with access to a spontaneous physical activity wheel, distributed into four subgroups: subjected a control diet (C); fed a leucine-rich diet (L); tumor-bearing rats (W); and tumor-bearing rats fed a leucine-rich diet (WL). All tumor-bearing rats were inoculated with 4x10⁶ viable Walker-256 carcinoma cells in the right flank subcutaneously. After euthanasia, the gastrocnemius muscle from the tumor’s opposite leg was collected and analyzed using NMR, with spectra profiled by Chenomx. Results were analyzed by Two-Way ANOVA followed by Tukey's post-hoc test and expressed as mean±standard deviation; at significance P<0.05.

Resultados

In the sedentary group, the WS showed increased levels of 3-hydroxybutyrate (BHB), IMP, and phenylalanine compared to the control group, while creatine phosphate, glutamine, glycine, and threonine were decreased. In the WLS group, glutamine and alanine content were reduced compared to the LS group, while BHB, isoleucine, and tyrosine increased. In the exercised groups, the WE showed decreased creatine phosphate and glutamine, with an increase in isoleucine, phenylalanine, tyrosine, and myo-inositol. In the WLE group, the creatine increased, while glutamine, BHB, and tyrosine decreased. Notably, when comparing sedentary and exercised groups, an inverse relationship between BHB and tyrosine was observed. In sedentary animals, both metabolites increased in the WL group compared to the L group, while in exercised animals, both decreased.

Conclusões

This reduction in the E group compared to the S group may suggest that combining nutritional supplementation with exercise can alter the metabolic process, leading to a decreased production of ketonic acids, suggesting a higher energy availability for these animals.

Financiador do resumo

FAPESP #2019/20558-2; #2017/02739-4; #2023/16369-5
CNPq #302997/2022-9

Palavras Chave

Physical exercise; Supplementation; Cancer cachexia