Abstract
Background: Cancer-cachexia induces a variety of metabolic disorders, including skeletal muscle imbalance. Alternative therapy, as nutritional supplementation with leucine, shows a modulatory effect over tumour damage in vivo and in vitro. Method: Adult rats distributed into Control (C), Walker tumour-bearing (W), control fed a leucine-rich diet (L), and tumour-bearing fed a leucine-rich diet (WL) groups had the gastrocnemius muscle metabolomic and proteomic assays performed in parallel to in vitro assays. Results: W group presented an affected muscle metabolomic and proteomic profile mainly related to energy generation and carbohydrates catabolic processes, but leucine-supplemented group (WL) recovered the energy production. In vitro assay showed that cell proliferation, mitochondria number and oxygen consumption were higher under leucine effect than the tumour influence. Muscle proteomics results showed that the main affected cell component was mitochondria, leading to an impacted energy generation, including impairment in proteins of the tricarboxylic cycle and carbohydrates catabolic processes, which were modulated and improved by leucine treatment. Conclusion: In summary, we showed a beneficial effect of leucine upon mitochondria, providing information about the muscle glycolytic pathways used by this amino acid, where it can be associated with the preservation of morphometric parameters and consequent protection against the effects of cachexia.
Highlights
Cachexia is a multifactorial syndrome that occurs in patients with cancer, heart failure, rheumatoid arthritis, obstructive pulmonary disease, and during chronic infections [1,2]
Our results showed that both tumour-bearing groups (W and which received leucine supplementation (WL)) had decreased body weight gain along experimental time in comparison to their respective control group (Table 1)
We found that leucine supplementation modulated pathways that favoured mitochondrial biogenesis in skeletal muscle tissue and cell, maintaining the energy production activity
Summary
Cachexia is a multifactorial syndrome that occurs in patients with cancer, heart failure, rheumatoid arthritis, obstructive pulmonary disease, and during chronic infections [1,2]. 9 million patients globally are affected by cachexia, and it is considered an indicative risk factor for death [3,4]. This syndrome leads to severe host tissue wasting and intense body weight loss, mainly due to both muscle mass loss and adipose tissue decrement. Results: W group presented an affected muscle metabolomic and proteomic profile mainly related to energy generation and carbohydrates catabolic processes, but leucine-supplemented group (WL) recovered the energy production. Muscle proteomics results showed that the main affected cell component was mitochondria, leading to an impacted energy generation, including impairment in proteins of the tricarboxylic cycle and carbohydrates catabolic processes, which were modulated and improved by leucine treatment. Conclusion: In summary, we showed a beneficial effect of leucine upon mitochondria, providing information about the muscle glycolytic pathways used by this amino acid, where it can be associated with the preservation of morphometric parameters and consequent protection against the effects of cachexia
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