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https://observatorio.fm.usp.br/handle/OPI/24206
Title: | A novel peptide that improves metabolic parameters without adverse central nervous system effects |
Authors: | RECKZIEGEL, Patricia; FESTUCCIA, William T.; BRITTO, Luiz R. G.; JANG, Karen L. Lopes; ROMAO, Carolina M.; HEIMANN, Joel C.; FOGACA, Manoela V.; RODRIGUES, Naielly S.; SILVA, Nicole R.; GUIMARAES, Francisco S.; EICHLER, Rosangela A. S.; GUPTA, Achla; GOMES, Ivone; DEVI, Lakshmi A.; HEIMANN, Andrea S.; FERRO, Emer S. |
Citation: | SCIENTIFIC REPORTS, v.7, article ID 14781, 11p, 2017 |
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. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MCM Artigos e Materiais de Revistas Científicas - LIM/16 Artigos e Materiais de Revistas Científicas - ODS/03 |
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art_RECKZIEGEL_A_novel_peptide_that_improves_metabolic_parameters_without_2017.PDF | publishedVersion (English) | 1.87 MB | Adobe PDF | View/Open |
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