Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats.
BACKGROUND
Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Conversely, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated.


METHODS
Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C--pregnant control, W--tumour-bearing, and P--pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L--pregnant leucine, WL--tumour-bearing, and PL--pair-fed, which received the same amount of food as ingested by the WL group.


RESULTS
The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2alpha and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced.


CONCLUSIONS
The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway.
Ventrucci
Gislaine
G
Laboratório de Nutrição e Câncer, Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, 13083-970, São Paulo, Brazil. ventrucci@hotmail.com <ventrucci@hotmail.com>
Mello
Maria Alice R
MA
Gomes-Marcondes
Maria Cristina C
MC
D000818:Animals; D002100:Cachexia / Q000178:diet therapy* / Q000209:etiology / Q000378:metabolism*; D002279:Carcinoma 256, Walker / Q000150:complications* / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D039642:Eukaryotic Initiation Factors / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007930:Leucine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D014176:Protein Biosynthesis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D039642:Eukaryotic Initiation Factors; D007328:Insulin; D007930:Leucine