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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A novel peptide that improves metabolic parameters without adverse central nervous system effects

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Author(s):
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Reckziegel, Patricia [1] ; Festuccia, William T. [2] ; Britto, Luiz R. G. [2] ; Lopes Jang, Karen L. [3, 4] ; Romao, Carolina M. [3, 4] ; Heimann, Joel C. [3] ; Fogaca, Manoela V. [5] ; Rodrigues, Naielly S. [5] ; Silva, Nicole R. [5] ; Guimaraes, Francisco S. [5] ; Eichler, Rosangela A. S. [1] ; Gupta, Achla [6] ; Gomes, Ivone [6] ; Devi, Lakshmi A. [6] ; Heimann, Andrea S. [4] ; Ferro, Emer S. [1]
Total Authors: 16
Affiliation:
[1] Univ Sao Paulo, Biomed Sci Inst, Dept Pharmacol, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Biomed Sci Inst, Dept Physiol & Biophys, BR-05508000 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Sch Med, Dept Internal Med, BR-01246903 Sao Paulo, SP - Brazil
[4] Proteimax Biotechnol LTDA, BR-05581001 Sao Paulo, SP - Brazil
[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil
[6] Icahn Sch Med Mt Sinai, Dept Pharmacol Sci, New York, NY 10029 - USA
Total Affiliations: 6
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 7, NOV 1 2017.
Web of Science Citations: 6
Abstract

Intracellular peptides generated by limited proteolysis are likely to function inside and outside cells and could represent new possibilities for drug development. Here, we used several conformational-sensitive antibodies targeting G-protein coupled receptors to screen for novel pharmacological active peptides. We find that one of these peptides, DITADDEPLT activates cannabinoid type 1 receptors. Single amino acid modifications identified a novel peptide, DIIADDEPLT (Pep19), with slightly better inverse agonist activity at cannabinoid type 1 receptors. Pep19 induced uncoupling protein 1 expression in both white adipose tissue and 3T3-L1 differentiated adipocytes; in the latter, Pep19 activates pERK1/2 and AKT signaling pathways. Uncoupling protein 1 expression induced by Pep19 in 3T3-L1 differentiated adipocytes is blocked by AM251, a cannabinoid type 1 receptors antagonist. Oral administration of Pep19 into diet-induced obese Wistar rats significantly reduces adiposity index, whole body weight, glucose, triacylglycerol, cholesterol and blood pressure, without altering heart rate; changes in the number and size of adipocytes were also observed. Pep19 has no central nervous system effects as suggested by the lack of brain c-Fos expression, cell toxicity, induction of the cannabinoid tetrad, depressive-and anxiety-like behaviors. Therefore, Pep19 has several advantages over previously identified peripherally active cannabinoid compounds, and could have clinical applications. (AU)

FAPESP's process: 15/20657-0 - Evaluation of hemopressin (HP) pharmacological use on obesity treatment
Grantee:Patrícia Reckziegel
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 16/04000-3 - Pharmacology of oligopeptidases and intracellular peptides
Grantee:Emer Suavinho Ferro
Support Opportunities: Research Projects - Thematic Grants