Transcriptome of brain nuclei involved in the control of energy homeostasis and hypothalamic-pituitary-adrenal axis activity in rats submitted to metabolic stress

• Grant number: 21/14506-0
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2023 - February 28, 2025
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Rodrigo César Rorato
• Grantee: Rodrigo César Rorato
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Andre de Souza Mecawi ; David Murphy

Abstract

The use of modern technologies that enable the identification of transcripts expressed in brain nuclei involved in the control of neuroendocrine and metabolic function can immensely contribute to the identification of potential therapeutic targets in the fight against different metabolic disorders. The therapies currently available to treat anorexia nervosa, HIV-related lipodystrophy, cachexia, obesity and diabetes are only modestly effective. Thus, studies aimed to identify brain genes that have their expression affected by metabolic state may allow for the development of new pharmacological and/or genetic therapies for metabolic diseases. We will focus our studies on hypothalamic and hindbrain nuclei that are well-recognized in the control of energy homeostasis, namely the paraventricular nucleus (PVN), the arcuate (ARC) nucleus, and the dorsal raphe nucleus (DRN). Comparing fed and fasted rats we will: obtain global transcriptome catalogues by RNASeq and identify differentially expressed genes (DEGs) responsive to energetic state. The DEGs identified by RNAseq will be validate by qPCR, RNAscope in situ hybridization and immunocytochemistry studies. Looking forward, we will to carry out pharmacological and/or gene-editing studies that will directly determine whether the new discovered genes contribute to the regulation of energy homeostasis. (AU)