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

Author(s)

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

• Document type: Journal article
• Source: CYTOKINE; v. 96, p. 253-260, AUG 2017.
• Web of Science Citations: 7

Abstract

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)

• FAPESP's process: 15/06766-0 - Nutrition and cancer: metabolomic and proteomic profile of muscle and tumor cell signaling pathways in vivo and in vitro assays under leucine nutritional supplementation
• Grantee: Bread Leandro Gomes da Cruz
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/08276-0 - Modultation of L-leucine on cell signaling and metabolic pathways of muscle protein metabolism in Walker 256 tumor-bearing rats.
• Grantee: Bread Leandro Gomes da Cruz
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/13334-7 - Nutrition and cancer: metabolomic, and proteomic profile of muscle, placental, fetal, and tumor cell signaling pathways in Walker-256 tumour-bearing pregnant rats submitted to leucine nutritional supplementation
• Grantee: Maria Cristina Cintra Gomes Marcondes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/16115-1 - Biochemical and molecular mechanisms of cachexia. effects of Walker factor and leucine supplementation on myotube cell culture
• Grantee: Maria Cristina Cintra Gomes Marcondes
• Support Opportunities: Regular Research Grants