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Intracellular peptides as modulators of thermogenesis-related metabolic pathways

Grant number: 19/25943-1
Support type:Research Grants - Young Investigators Grants
Duration: November 01, 2020 - October 31, 2025
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Patrícia Reckziegel
Grantee:Patrícia Reckziegel
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Emer Suavinho Ferro ; Gustavo José da Silva Pereira ; William Tadeu Lara Festuccia

Abstract

Brown adipose tissue (BAT) is thermogenic due to the presence of mitochondrial-rich adipocytes with a high amount of mitochondrial uncoupling protein 1 (UCP1), a protein that dissipates energy from ATP synthesis for heat production. Under certain stimulus, white adipose tissue (WAT) cells may exhibit brown adipocyte characteristics in a process called browning. BAT activation and browning have been shown to be promising in the treatment of obesity and associated diseases, largely due to increased energy metabolism, glucose and triglyceride uptake. Intracellular peptides have been shown to be modulators of various pathways related to energy metabolism, they are probably differently present in BAT and WAT tissues, as well as during BAT activation and browning processes, exerting modulatory effects. Given this, the present study aims to investigate the in vitro and in vivo biological effects of intracellular peptides identified in BAT and WAT samples from mice under thermogenic stimulation. For this, intracellular peptides will be identified from adipose tissues of mice exposed to thermoneutral conditions (30ºC) or cold (4°C) and treated with vehicle or pioglitazone (PPAR³ agonist) for 15 days. Histological, gene and protein expression analyzes should prove BAT activation and browning in these animals. Peptidomic analysis will innovatively identify the intracellular peptide content of BAT and inguinal WAT samples, and the peptides altered in the thermogenic process. Some of these peptides will be selected and synthesized for in vitro studies in primary culture of brown and white adipocytes. Peptides that will positively modulate thermogenic-related parameters in vitro will be investigated in obese mice and a detailed metabolic analysis will be performed with these obese animals. Thus, we intended to characterize the role of intracellular peptides in BAT versus WAT, to verify the main points where intracellular peptides can modulate thermogenesis, and to identify new biological peptides with potential for the treatment of obesity and associated diseases. (AU)