Evaluation of hemopressin (HP) pharmacological use on obesity treatment

• Grant number: 15/20657-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date until: March 01, 2016
• End date until: July 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Emer Suavinho Ferro
• Grantee: Patrícia Reckziegel
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 17/08850-4 - Are metabolic effects of PFCs mediated by activation of brown adipose tissue?, BE.EP.PD

Abstract

Obesity prevalence has shown increasingly alarming and growing in the world population. The control of obesity through diet and physical activity is often unsatisfactory, and the available drugs usually have several side effects. Antagonists of cannabinoid receptor type 1 (CB1) play an important role in the pharmacological management of obesity. Recent findings have shown that white adipose tissue can differentiate into brown (knowing as "browning"), raising the basal energy metabolism and promoting weight loss. It has been suggested that CB1 inverse agonists may promote browning too. Our research group works with the identification of intracellular peptides and, among them hemopressin (HP) is a potent inverse agonist of CB1 receptors. This project aims to evaluate the potential pharmacological use of HP for the treatment of obesity. Initially this hypothesis will be addressed in cell culture evaluating the HP's ability to activate mitochondrial uncoupling protein 1 (UCP-1). Additionally, the effects of HP on the energy metabolism of mice will be addressed by analyzing food intake, body weight, blood markers, adipose tissue morphology, activation of UCP-1 and markers of inflammation in adipose tissue (brown and white), and evaluating temperature by calorimetry. Further analysis will be conducted in obese mice treated with HP. Side effects such as anxiety and depression, and cardiovascular changes will also be investigated. It is expected that HP can induce weight loss of the animals due to action on CB1 and stimulation of browning without providing central or cardiovascular side effects that limit cannabinoid inverse agonists for the treatment of obesity. The results of this study may open new pharmacological avenues for treating obesity using intracellular peptides.

Scientific publications

(4)

(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)

GEWEHR, MAYARA C. F.; TEIXEIRA, ALEXANDRE A. S.; SANTOS, BRUNA A. C.; BIONDO, LUANA A.; GOZZO, FABIO C.; CORDIBELLO, AMANDA M.; EICHLER, ROSANGELA A. S.; RECKZIEGEL, PATRICIA; DA SILVA, RENEE N. O.; DOS SANTOS, NILTON B.; et al. The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity. BIOMOLECULES, v. 10, n. 2, FEB 2020. (14/17264-3, 16/04000-3, 04/04933-2, 15/20657-0)

DOS SANTOS, NILTON B.; FRANCO, ROSEANE D.; CAMARINI, ROSANA; MUNHOZ, CAROLINA D.; EICHLER, ROSANGELA A. S.; GEWEHR, MAYARA C. F.; RECKZIEGEL, PATRICIA; LLANOS, RICARDO P.; DALE, CAMILA S.; DA SILVA, VICTORIA R. O.; et al. Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization. BIOMOLECULES, v. 9, n. 8, AUG 2019. (16/04000-3, 15/07273-8, 04/04933-2, 15/20657-0)

GEWEHR, MAYARA C. F.; SILVERIO, RENATA; ROSA-NETO, JOSE CESAR; LIRA, FABIO S.; RECKZIEGEL, PATRICIA; FERRO, EMER S.. Peptides from Natural or Rationally Designed Sources Can Be Used in Overweight, Obesity, and Type 2 Diabetes Therapies. Molecules, v. 25, n. 5, MAR 1 2020. (16/04000-3, 15/20657-0)

RECKZIEGEL, PATRICIA; FESTUCCIA, WILLIAM T.; BRITTO, LUIZ R. G.; LOPES JANG, KAREN L.; ROMAO, CAROLINA M.; HEIMANN, JOEL C.; FOGACA, MANOELA V.; RODRIGUES, NAIELLY S.; SILVA, NICOLE R.; GUIMARAES, FRANCISCO S.; et al. A novel peptide that improves metabolic parameters without adverse central nervous system effects. SCIENTIFIC REPORTS, v. 7, NOV 1 2017. (15/20657-0, 16/04000-3)