Leucine-rich Diet Improved Muscle Function in Cachectic Walker 256 Tumor-bearing Wistar Rats

Abstract

Background: Skeletal muscle atrophy occurs in several pathological conditions such as cancer, a condition termed cancer cachexia. This condition is associated with an increase in morbidity and poor treatment response, decreasing quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy preventing muscle atrophy in cancer cachexia hosts. Besides muscle atrophy, muscle function loss is even more important to the patient’s quality of life. Therefore, this study aimed to evaluate the effects of leucine-rich diet on muscle function activity of cachectic Walker 256 tumor-bearing rats and to correlate such effects with molecular pathways of muscle atrophy. Methods: Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet: Control (C) and Walker 256 tumor-bearing (W), and two other groups were fed with a leucine-rich diet: Leucine Control (L) and Leucine Walker 256 tumor-bearing (LW). The functional analysis (walking, behavior, and strength tests) was measured and before and after tumor inoculation. Cachexia parameters such as body weight loss, muscle and fat mass, pro-inflammatory cytokine profile, and molecular and morphological aspects of skeletal muscle were also performed. Results: Walker 256 tumor growth led to muscle function decline, cachexia manifestation symptoms, muscle fiber cross-section area reduction, associated with the altered morphological pattern and classical muscle protein degradation pathway activation, with up-regulation of FoXO1, MuRF1, and 20S proteins. On the other hand, a leucine-rich diet improved muscle strength while reducing the decline of walking and behavior, partially improving the cachexia manifestations and preventing muscle atrophy and protein degradation in Walker 256 tumor-bearing rats. Conclusions: A leucine-rich diet diminished muscle protein degradation and enhanced oxidative pathways, leading to better muscle functional performance.