title: Leucine-rich diet alters the1H-NMR based metabolomic profile without changing the Walker-256 tumour mass in rats.
abstract: Cachexia is one of the most important causes of cancer-related death. Supplementation with branched-chain amino acids, particularly leucine, has been used to minimise loss of muscle tissue, although few studies have examined the effect of this type of nutritional supplementation on the metabolism of the tumour-bearing host. Therefore, the present study evaluated whether a leucine-rich diet affects metabolomic derangements in serum and tumour tissues in tumour-bearing Walker-256 rats (providing an experimental model of cachexia).
  
  
  
  After 21 days feeding Wistar female rats a leucine-rich diet, distributed in L-leucine and LW-leucine Walker-256 tumour-bearing groups, we examined the metabolomic profile of serum and tumour tissue samples and compared them with samples from tumour-bearing rats fed a normal protein diet (C - control; W - tumour-bearing groups). We utilised1H-NMR as a means to study the serum and tumour metabolomic profile, tumour proliferation and tumour protein synthesis pathway.
  
  
  
  Among the 58 serum metabolites examined, we found that 12 were altered in the tumour-bearing group, reflecting an increase in activity of some metabolic pathways related to energy production, which diverted many nutrients toward tumour growth. Despite displaying increased tumour cell activity (i.e., higher Ki-67 and mTOR expression), there were no differences in tumour mass associated with changes in 23 metabolites (resulting from valine, leucine and isoleucine synthesis and degradation, and from the synthesis and degradation of ketone bodies) in the leucine-tumour group. This result suggests that the majority of nutrients were used for host maintenance.
  
  
  
  A leucine rich-diet, largely used to prevent skeletal muscle loss, did not affect Walker 256 tumour growth and led to metabolomic alterations that may partially explain the positive effects of leucine for the whole tumour-bearing host.
authors.affiliation: Department of Structural and Functional Biology, Laboratory of Nutrition and Cancer, Institute of Biology, University of Campinas-UNICAMP, Campinas, 13083862, São Paulo, Brazil.
authors.forename: Laís Rosa
authors.initials: LR
authors.lastname: Viana
authors.affiliation: Brazilian Biosciences National Laboratory, Campinas, São Paulo, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Canevarolo
authors.affiliation: Department of Structural and Functional Biology, Laboratory of Nutrition and Cancer, Institute of Biology, University of Campinas-UNICAMP, Campinas, 13083862, São Paulo, Brazil.
authors.forename: Anna Caroline Perina
authors.initials: AC
authors.lastname: Luiz
authors.affiliation: Department of Structural and Functional Biology, Laboratory of Nutrition and Cancer, Institute of Biology, University of Campinas-UNICAMP, Campinas, 13083862, São Paulo, Brazil.
authors.forename: Raquel Frias
authors.initials: RF
authors.lastname: Soares
authors.affiliation: Department of Structural and Functional Biology, Laboratory of Nutrition and Cancer, Institute of Biology, University of Campinas-UNICAMP, Campinas, 13083862, São Paulo, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Lubaczeuski
authors.affiliation: Brazilian Biosciences National Laboratory, Campinas, São Paulo, Brazil.
authors.forename: Ana Carolina de Mattos
authors.initials: AC
authors.lastname: Zeri
authors.affiliation: Department of Structural and Functional Biology, Laboratory of Nutrition and Cancer, Institute of Biology, University of Campinas-UNICAMP, Campinas, 13083862, São Paulo, Brazil. cintgoma@unicamp.br.
authors.forename: Maria Cristina Cintra
authors.initials: MC
authors.lastname: Gomes-Marcondes
mesh_terms: D000818:Animals; D002100:Cachexia / Q000097:blood / Q000178:diet therapy* / Q000209:etiology; D045744:Cell Line, Tumor; D004032:Diet; D005260:Female; D007930:Leucine / Q000008:administration & dosage*; D055442:Metabolome; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000097:blood* / Q000150:complications / Q000473:pathology; D017208:Rats, Wistar; D047368:Tumor Burden
chemical_list: D007930:Leucine
keywords: Cancer cachexia; Leucine supplementation; Metabolic derangements; Metabolomic; Walker 256 tumour