Effects of a leucine-rich diet and exercise on glycolytic enzyme gene expression in the muscle of tumour-bearing rats

• Grant number: 13/01322-1
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: April 01, 2013
• End date: July 31, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Cristina Cintra Gomes Marcondes
• Grantee: Maria Cristina Cintra Gomes Marcondes
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Background:The intense mobilisation of substrates during cancer induces a loss of body mass, leading to cachexia. Cachexia promotes intense involuntary weight loss, which mainly results from the depletion of muscle protein due to increased proteolysis and/or decreased protein synthesis. Leucine is used as an energy source by skeletal muscle, as a precursor of gluconeogenesis and as a cell-signalling molecule. Additionally, physical activity increases glucose consumption, which reduces the levels of circulating glucose and insulin. Therefore, this work investigated the effects of leucine supplementation and physical exercise on carbohydrate metabolism in muscle tissue under the effects of Walker tumour growth. Methods:Trained adult rats were fed a leucine-rich diet and implanted with Walker-256 tumour cells. We assessed the levels of serum glucose, cytokines and hormones and muscle glycolytic gene expression, glycogen content and fibre size. Results: The data presented here clearly show that tumour growth produced deleterious effects on tumour-bearing rats, increasing serum cytokines (pro-inflammatory TNF-a, INF-g and IL-6, anti-inflammatory IL-4 and IL-10 and the IL-10/TNF-a ratio) and reducing serum glucose and insulin. Tumour growth induced a decrease in muscle GLUT4 expression and increased muscle pyruvate dehydrogenase (PDH), lactate dehydrogenase (LDH), and monocarboxylic acid transporter 1 (MCT1) expression; it also reduced muscle glycogen content and muscle fibre. Conclusions: Leucine supplementation alone or combined with exercise benefited the host tissues, improving the muscle glucose metabolism, as illustrated by the reduction of serum pro-inflammatory cytokines levels and the maintenance of GLUT4, hexokinase, PDH, LDH and MCT1 expression. These changes all improved muscle glycogen content, which consequently benefited the tumour-bearing host. (AU)