Can peptides derived from the UCP1 protein modulate parameters related to thermogenesis in white and brown adipocytes?

• Grant number: 23/02579-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Patrícia Reckziegel
• Grantee: Giovanna Freitas Rodrigues Jardim
• 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): 24/16709-3 - The mystery of UCP1 negative adipocytes present in brown and beige adipose tissues of cold-acclimated mice, BE.EP.IC

Abstract

The thermogenic capacity of the brown (BAT) and beige adipose tissue involves the differential expression of mitochondrial uncoupling protein type 1 (UCP1). The UCP1 is located at the internal mitochondrial membrane of brown and beige adipocytes where it dissipates the proton gradient from ATP synthesis to heat production, increasing the energy expenditure and the uptake of glucose and triglycerides by cells. Our research group, during a screening of peptides present in BAT and beige samples of animals exposed to cold and treated with pioglitazone, identified, in a novel way, peptides derived from UCP1. Thus, the present project aims to investigate if those peptides derived from UCP1 can modulate parameters related to the thermogenesis of adipocytes in vitro. Primary cultures of brown and white adipocytes will be exposed to the peptides of interest and used for analyses of gene and protein expression of thermogenesis and adipogenesis-related markers. In addition, peptides derived from the adipogenesis protein FABP4 and identified on beige adipose tissue will be evaluated. The peptides will be tested with and without a TAT group for the analysis of their effects at extra and intracellular space, respectively.Furthermore, the effects of the peptides will be evaluated on the absence and the presence of an adrenergic stimulus (with norepinephrine). In this way, we hope to advance the understanding of whether intracellular peptides have a function related to their related protein, especially UCP1. It is possible that these peptides studied may represent possible therapeutic targets for obesity and associated diseases.