ID: 47: Nutritional L-leucine supplementation modulates muscle protein wasting and pro-inflammatory cytokines in Walker-256 tumour-bearing rats

Abstract

Cancer cachexia is characterised by involuntary weight loss; the maintenance of lean body mass in cachectic hosts may contribute to a reduction in the number of deaths and an overall improvement in quality of life. The branched chain amino acid leucine affects cell signalling, thereby leading to an improvement in lean body mass by decreasing muscle protein degradation. We assess the effects of a leucine-rich diet on protein degradation signalling in muscle over the course of tumour growth. Adult Wistar rats were distributed into experimental groups according to whether a tumour or not was inoculated and whether or not a leucine-rich diet was provided. The animals were subsequently sacrificed at three different time points during tumour evolution (7th, 14th and 21st day after tumour implant). Protein degradation signalling, as indicated by ubiquitin–proteasome subunits (11S, 19S and 20S), and pro- and anti-inflammatory cytokines were analysed in each of the experimental groups. Tumour growth promoted a decrease in muscle protein, a sharp increase in pro-inflammatory cytokines (TNF α , IL-6 and IFN γ ) and a progressive increase in proteasome subunits (19S and 20S). Thus, the role of leucine in this specific situation reveals an increased process mainly on the 14th day after tumour implantation and a modulated action on the 21st day of tumour growth. The results indicate that leucine in the diet modulates some important key aspects of the proteasome pathway and inflammatory process in the cancer cachexia state.