Effect of a leucine-supplemented diet on body composition changes in pregnant rats bearing Walker 256 tumor

Abstract

Cancer patients present high mobilization of host protein, with a decrease in lean body mass and body fat depletion occurring in parallel to neoplastic growth. Since leucine is one of the principal amino acids used by skeletal muscle for energy, we investigated the changes in body composition of pregnant tumor-bearing rats after a leucinesupplemented diet. Sixty pregnant Wistar rats divided into six groups were fed a normal protein diet (18%, N) or a leucine-supplemented diet (3% L-leucine, L). The pregnant groups were: control (CN), Walker 256 carcinoma-bearing rats (WN), control rats pair-fed with tumor-bearing rats (pfN), leucine-supplemented (CL), leucine-supplemented tumor-bearing (WL), and leucine-supplemented rats pair-fed with tumor-bearing rats (pfL). At the end of pregnancy, all animals were sacrificed and body weight and tumor and fetal weight were determined. The carcasses were then analyzed for water, fat and total, collagen and non-collagen nitrogen content. Carcass weight was reduced in the WN, WL, pfN and pfL groups compared to control. The lean body mass and total carcass nitrogen were reduced in both tumorbearing groups. Despite tumor growth and a decrease in fetal weight, there was a slight decrease in collagen (7%) and non-collagen nitrogen (8%) in the WL group compared with the WN group which showed a decrease of 8 and 12%, respectively. Although the WL group presented severe tumor growth effects, total carcass nitrogen and noncollagen nitrogen were particularly higher in this leucine-supplemented group compared to the WN group. These data suggest that the leucine-supplemented diet had a beneficial effect, probably attenuating body wasting.

A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats

“…Although weight loss is commonly associated with a decrease in food intake, anorexia does not appear to be responsible for the cachectic process. Depletion of host fat stores is a common characteristic of Walker 256 tumor-bearing rats, which was also observed in the present study and has been observed in other experimental tumor-bearing models involving severe weight loss (9,12). In an extensive review, Tisdale (1) reported that the loss of body fat was related, in part, to an increase in glycerol and fatty-acid turnover, leading to increased lipolysis and to a circulatory lipid-mobilizing factor found in both animal and human cachectic hosts.…”

“…Other studies have also demonstrated a similar alteration in body water content in pregnant tumor-bearing rats (9) and in tumor-bearing male rats (12). Besides the profound decrease in body fat, Walker 256 carcinosarcoma-bearing rats showed a significant decrease of about 15% in lean tissue mass in comparison to control groups (9,12).…”

“…Other studies have also demonstrated a similar alteration in body water content in pregnant tumor-bearing rats (9) and in tumor-bearing male rats (12). Besides the profound decrease in body fat, Walker 256 carcinosarcoma-bearing rats showed a significant decrease of about 15% in lean tissue mass in comparison to control groups (9,12). In contrast, studies on interleukin-6-secreting tumor-bearing mice demonstrated a significant loss in fat tissue without loss of lean body mass or water content (13).…”

“…The lean carcass mass was calculated by subtracting dry carcass without fat from dry carcass including fat. The determination of chemical whole body composition followed the methodology of Ventrucci et al (9). Results are reported as mean ± SEM and were analyzed with the Graph Pad Prism program, v3.00 for Windows 98.…”

A Leucine-Rich Diet Modulates the Tumor-Induced Down-Regulation of the MAPK/ERK and PI3K/Akt/mTOR Signaling Pathways and Maintains the Expression of the Ubiquitin-Proteasome Pathway in the Placental Tissue of NMRI Mice1

“…Leucine regulates protein synthesis in skeletal muscles following food intake, stimulating the mTOR pathway and inhibiting the ubiquitin-proteasome pathway. A leucine-rich diet can improve carcass nitrogen levels and lean body mass in both Walker 256 tumor-bearing rats and MAC16 adenocarcinoma-bearing mice [1,[24][25][26][27][28]. Both of these tumors are experimental models of cachexia [29]; for this reason, we chose to use the MAC16 tumor in this work to investigate the metabolic and biochemical changes associated with pregnancy in order to characterize these effects.…”