Role of adipose tissue in inflammatory response during cancer cachexia

• Grant number: 09/53259-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2010
• End date: February 28, 2011
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marilia Cerqueira Leite Seelaender
• Grantee: Mireia Olivan Riera
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cachexia is defined as a state of ill health, malnutrition and physical wasting with loss of weight and muscle (up to 80% of both adipose tissue and skeletal muscle mass), usually caused by chronic disease. Cancer cachexia occurs in varying degrees of severity in about half of patients with malignancy and is associated with more than 20% of cancer deaths. The emerging view is that cachexia of cancer is mainly due to major metabolic abnormalities. These are caused predominantly by cytokines released by the immune system as a response to the presence of the cancer (tumour necrosis factor alpha, interferon gamma and interleukins 1 and 6). Also tumour products have also been identified (such as lipolytic hormones), These factors cause profound lipolysis, negative nitrogen balance and anorexia. TNFα, a proinflammatory cytokines also called cachectin, was identified as a molecule responsible for the induction of cachexia seen in chronic illnesses such as cancer and sustained infection. Due to the conception of this syndrome as a chronic inflammatory state, in which the host's reaction to the presence of the tumour seems to be the main cause agent, in this study we want investigate the contribution of the adipose tissue to the systemic inflammation associated to cancer cachexia and the heterogeneous aspects of this tissue (physiology, morphology and response to the disease) analyzing gene expression of different kind of cytokines and transcript factors implicated in the development of cachexia. (AU)