Identification of intracellular peptides and their relationship with thermogenesis: An omics approach

• Grant number: 24/02202-4
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Interdisciplinary Subjects
• Agreement: CNPq
• Principal Investigator: Patrícia Reckziegel
• Grantee: Patrícia Reckziegel
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/25943-1 - Intracellular peptides as modulators of thermogenesis-related metabolic pathways, AP.JP
• Associated scholarship(s): 24/13521-3 - Identification of intracellular peptides and their relationship with thermogenesis: An "omics" approach, BP.JD

Abstract

Brown adipose tissue (BAT) is known for its thermogenic function due to the expression of mitochondrial uncoupling protein 1 (Ucp1). Under certain conditions, white adipose tissue (WAT) can express Ucp1, acquiring thermogenic characteristics through a phenomenon known as browning. The activation of BAT and browning process have been considered effective strategies in combating obesity and related metabolic disorders due to an increase in basal energy consumption and enhanced glucose and triglyceride uptake by cells. Intracellular peptides have been shown to modulate various metabolic pathways. Preliminary results from the Auxílio Jovem Pesquisador FAPESP indicate distinct profiles of intracellular peptides between BAT and WAT, and during the thermogenic process. Bioinformatics tools could assist in analyzing these data. The current project aims to explore the biological effects of the intracellular peptide profile in BAT and WAT samples from mice under thermogenic stimulus. For this, the intracellular peptide profile identified in adipose tissues from mice exposed to thermoneutrality conditions (21°C) or cold (7°C), and treated with vehicle or pioglitazone (a PPAR³ agonist) for 15 days will be analyzed using various bioinformatics tools. Different computational/statistical approaches will be employed for both peptides and the proteins of origin, such as: 1) identification of the biological processes affected by these peptides; 2) analysis of co-expression modules to visualize sets of peptides that behave similarly under different conditions; and 3) machine learning algorithms will be used for the prediction of the most representative intracellular peptides within each experimental group. Finally, we will perform a primary culture of brown and white adipose cells, analyze the peptide profile, and compare this profile with the data obtained by peptidomics obtained in the tissues in previous analyses. Thus, the study intends to characterize the role of intracellular peptides in BAT versus WAT, to identify key points where these peptides modulate thermogenesis, and to discover new peptide compounds with potential for the treatment of obesity and associated diseases. (AU)