Effects of metformin treatment associated to leucine rich-diet on protein metabolism in Walker 256 tumour-bearing rats

Author(s)

André Gustavo de Oliveira

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2011-07-13

Examining board members

Maria Cristina Cintra Gomes Marcondes; Miguel Arcanjo Areas; José Barreto Campello Carvalheira

• Advisor: Maria Cristina Cintra Gomes Marcondes

Abstract

Tumour growth induces cachexia by intense nutrient waste, characterized by involuntary host weight loss, mainly depleting the total body protein and fat. mTOR signaling pathway controls the cell growth regulating translation of mRNA, and the inhibition of this pathway by compounds such as metformin (M) could decrease tumour growth rate. Knowing these facts, the aim of this study was to evaluate metformin effects associated to leucine-rich diet in Walker 256 (W) tumour-bearing animals, on muscle protein metabolism, trying to improve the cachectic state. Young male Wistar rats were distributed into 8 groups, according to the tumour implant, the treatment with metformin (36 mg x kg-1) and/or leucine-rich diet (3% leucine). After the sacrifice of the animals we evaluated some somatic and biochemical parameters as well as the muscle cell signaling pathways.. Tumour growth promotes 20%reduction of body mass and 70% of fat mass. Glucose serum was 50% decreased and also the total serum proteins (20% less) and albumin (25% reduced). GH and IGF-1 concentrations were decreased in all tumour-bearing groups, while ACTH concentration was increased. Tumour-bearing groups had higher protein degradation rates while protein synthesis rates were not changed, showing decreased protein turnover. Leucine rich-diet stimulated protein synthesis in non-tumour-bearing groups and these results suggest that this effect was through Akt or Erk pathways and metformin stimulated signaling through IRS-1, leading to Erk activation. Tumour growth promoted lean body mass spoliation and modulated protein synthesis through Erk and IRS-1 inhibition. Leucine-rich diet was able to stimulate protein synthesis in non tumour-bearing animals, although the treatment with metformina was not thus effective in decreasing tumour's cells growth, probably by low dose concentration (AU)

• FAPESP's process: 08/07737-0 - Effects of metformin treatment associated to leucine rich-diet on protein metabolism in tumour-bearing rats
• Grantee: André Gustavo de Oliveira
• Support Opportunities: Scholarships in Brazil - Master