Knockout mice for thimet oligopeptidase as a model for the study of Obesity and Obesity-associated diseases

• Grant number: 19/27149-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2020
• End date: November 30, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Emer Suavinho Ferro
• Grantee: Mayara Calegaro Ferrari Gewehr
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/04000-3 - Pharmacology of oligopeptidases and intracellular peptides, AP.TEM

Abstract

Obesity represents a major public health problem given its high prevalence and increased risk for the development of other diseases such as Heart Disease, Diabetes Mellitus, and various Cancers. The steady increase in the overweight and obese population creates opportunities for therapeutic innovation with the aim of improving their quality of life. In the present project, C57BL6 knockout mice for thimet oligopeptidase (THOP1-/-) will be investigated for resistance to Obesity and associated diseases. Wild C57BL6 (WT) and THOP1-/- will be fed a standard (SD) or hyperlipid (DH) diet for a period of 24 weeks. Both WT and THOP1-/- mice will be monitored for blood glucose, insulin resistance, cholesterolemia, fat levels in adipose and liver tissues, lipolytic activity following adrenergic stimulation in adipose tissue, and endurance in high running tests. treadmill intensity. THOP1-/- mice will be compared to WT for possible changes in the expression levels of Obesity-specific genes and microRNAs, as well as the relative levels of intracellular peptides in inguinal adipose tissue. Some of these possibly altered peptides will be synthesized and tested for activity on Obesity-associated gene and microRNA expression levels in 3T3L1 adipocytes. Taken together, the results of this application will suggest whether intracellular peptides are important modulators of Obesity related parameters. In addition, these results will indicate a possible connection between proteasome protein degradation and gene expression. Consequently, these results may propose that THOP1 and intracellular peptides may represent new therapeutic targets for the control of Obesity and associated diseases. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PARADA, CAROLINA A.; DE OLIVEIRA, IVAN PIRES; GEWEHR, MAYARA C. F.; MACHADO-NETO, JOAO AGOSTINHO; LIMA, KELI; EICHLER, ROSANGELA A. S.; LOPES, LUCIA R.; BECHARA, LUIZ R. G.; FERREIRA, JULIO C. B.; FESTUCCIA, WILLIAM T.; et al. ffect of FKBP12-Derived Intracellular Peptides on Rapamycin-Induced FKBP-FRB Interaction and Autophag. ELL, v. 11, n. 3, FEB 2022. (19/25049-9, 13/07937-8, 19/27149-0, 17/02201-4, 16/04000-3, 19/07332-5, 19/23864-7)