L-leucine dietary supplementation modulates muscle protein degradation and increases pro-inflammatory cytokines in tumour-bearing rats

Autor(es)

Cruz, Bread ; Oliveira, Andre ; Cintra Gomes-Marcondes, Maria Cristina

• Tipo de documento: Artigo Científico
• Fonte: CYTOKINE; v. 96, p. 253-260, AUG 2017.
• Citações Web of Science: 7

Resumo

Cancer cachexia is characterised by involuntary weight loss associated with systemic inflammation and metabolic changes. Studies aimed at maintaining lean body mass in cachectic tumour-bearing hosts have made important contributions reducing the number of deaths and improving the quality of life. In recent years, leucine has demonstrated effective action in maintaining lean body mass by decreasing muscle protein degradation. Currently, there is a growing need to understand how leucine stimulates protein synthesis and acts protectively in a cachectic organism. Thus, this study aimed to assess the effects of a leucine-rich diet on protein degradation signalling in muscle over the course of tumour growth. Animals were distributed into four experimental groups, which did or did not receive 2 x 10(6) viable Walker-tumour cells. Some were fed a leucine-rich diet, and the groups were subsequently sacrificed at three different time points of tumour evolution (7th, 14th, and 21st days). Protein degradation signals, as indicated by ubiquitin-proteasome subunits (11S, 19S, and 20S) and pro- and anti-inflammatory cytokines, were analysed in all experimental groups. In tumour-bearing animals without nutritional supplementation (W7, W14, and W21 groups), we observed that the tumour growth promoted a concurrent decrease in muscle protein, a sharp increase in pro-inflammatory cytokines (TNF alpha, IL-6, and IFN gamma), and a progressive increase in proteasome subunits (19S and 20S). Thus, the leucine-supplemented tumour bearing groups showed improvements in muscle mass and protein content, and in this specific situation, the leucine-rich diet led to an increase on the day in cytokine profile and proteasome subunits mainly on the 14th day, which subsequently had a modulating effect on tumour growth on the 21st day. These results indicate that the presence of leucine in the diet may modulate important aspects of the proteasomal pathway in cancer cachexia and may prevent muscle wasting due to the decrease in the cachexia index. (AU)

• Processo FAPESP: 15/06766-0 - Nutrição e câncer: avaliação do perfil metabolômico, proteômico e de vias de sinalização celular em músculo esquelético e tecido tumoral sob influência da suplementação de leucina durante o desenvolvimento in vitro e in vivo do Tumor de Walker
• Beneficiário: Bread Leandro Gomes da Cruz
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/08276-0 - Ação in vivo de L-leucina sobre sinalização celular e vias metabólicas durante o metabolismo protéico muscular em ratos portadores de tumor Walker 256
• Beneficiário: Bread Leandro Gomes da Cruz
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/13334-7 - Nutrição e câncer: avaliação do perfil metabolômico, proteômico e das vias de sinalização celular muscular, placentária e fetal e do tecido tumoral sob influência dos hormônios da gravidez em ratas
• Beneficiário: Maria Cristina Cintra Gomes Marcondes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/16115-1 - Estudo dos mecanismos bioquímicos e moleculares da caquexia: avaliação dos efeitos do fator Walker (FW) e da leucina em cultura celular de miotúbulos (células C2C12)
• Beneficiário: Maria Cristina Cintra Gomes Marcondes
• Modalidade de apoio: Auxílio à Pesquisa - Regular