The role of the hypothalamic mTOR pathway in cachectic AH-130 tumor bearing rats

• Grant number: 19/07595-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): December 01, 2019
• Effective date (End): November 30, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marilia Cerqueira Leite Seelaender
• Grantee: Amanda Soares Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cachexia is a multifactorial syndrome associated with underlying disease, such as cancer. It is characterized by involuntary loss of skeletal muscle mass, anorexia and marked systemic inflammation. The observed changes are caused by several factors such as cytokines, secreted by the host itself due to metabolic alterations. Studies reported that systemic inflammation leads to central nervous system function's dysregulation and neuroinflammation causing disrupted food behavior and body composition changes. Thus, the central nervous system (CNS) may have an important role in the pathogenesis of cachexia. However, CNS role in cachexia remains unclear. Due to the central role of rapamycin pathway (mTOR) related to anabolic processes that are part of body composition homeostasis, such as the synthesis proteins and lipids. The activation of mTOR pathway in the arcuate nucleus of the hypothalamus could induce anorexia and cachexia in response to central inflammation. This project aims to evaluate the role of the mTOR pathway in neuroinflammation in cachectic rats. 14 Wistar male rats will be analyzed and divided into 2 groups: control and AH-130 (tumor-bearing Yoshida AH-130). The experimental protocol will be to analyze the pathway in the hypothalamus by gene expression and protein determination techniques, with the perspective of elicidate possible changes related to cachexia. It is a translational study in which results will be compared with CNS images of cachectic patients acquired by magnetic resonance, referring to the Fapesp project noº 2016/12508-7.