Role of chemerin/ChemR23 system on insulin signalling in adipocytes and arteries of db/db mice

• Grant number: 15/01630-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: May 01, 2015
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Ana Maria de Oliveira
• Grantee: Karla Bianca Neves
• Supervisor: Rhian M. Touyz
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Glasgow, Scotland
• Associated to the scholarship: 12/13144-8 - Effects of the adipokine Chemerin on the Responsiveness to Insulin Mesenteric Arteries of Mice, BP.DR

Abstract

The adipose tissue produces many adipokines, including chemerin, a chemoattractant molecule that mediates its effect through a G protein-coupled receptor, ChemR23. Chemerin has been linked to vascular endothelial dysfunction, inflammation and insulin resistance, key contributors to several disease processes, including obesity, diabetes and arterial hypertension. Considering that db/db mice, an experimental model of type 2 diabetes, exhibit augmented levels of chemerin, endothelial dysfunction, inflammation and insulin resistance, the aim of the present study is to determine the effects of chemerin/ChemR23 inhibition on endothelial function, inflammation and insulin signalling in db/db mice. We hypothesized that chemerin, through its own receptor, impairs insulin signalling in adipocytes and vascular cells of db/db mice and that chemR23 antagonism will decrease the abnormalities in the vascular and adipocytes responses to insulin. Male db/db mice and their nondiabetic controls (db/m) will be used. Db/db mice will be treated with CCX 832 (chemR23 antagonist) or vehicle and insulin signalling in adipocytes and arteries will be studied. In addition, vascular structure and function will be determined in mesenteric arteries from these animals by using pressure and wire myographs. Histological analyses will be performed in adipose tissue to evaluate morphological/structural changes and pro-inflammatory markers. Expression of proteins involved in redox, inflammatory processes and insulin signalling will also be determined. This study will further dissect the role of chemerin/chemR23 on insulin signaling and on diabetes-associated vascular complications. (AU)

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)

NEVES, KARLA BIANCA; MONTEZANO, AUGUSTO CESAR; ALVES-LOPES, RHEURE; BRUDER-NASCIMENTO, THIAGO; COSTA, RAFAEL MENEZES; COSTA, ROBERTO S.; TOUYZ, RHIAN M.; TOSTES, RITA C.. Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 8, p. 15-pg., 2018-08-01. (15/01630-3, 13/08216-2, 12/13144-8)

NEVES, KARLA BIANCA; MONTEZANO, AUGUSTO CESAR; ALVES-LOPES, RHEURE; BRUDER-NASCIMENTO, THIAGO; COSTA, RAFAEL MENEZES; COSTA, ROBERTO S.; TOUYZ, RHIAN M.; TOSTES, RITA C.. Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 8, AUG 2018. (13/08216-2, 15/01630-3, 12/13144-8)

NEVES, KARLA BIANCA; CAT, AURELIE NGUYEN DINH; ALVES-LOPES, RHEURE; HARVEY, KATIE YATES; DA COSTA, RAFAEL MENEZES; LOBATO, NUBIA SOUZA; MONTEZANO, AUGUSTO CESAR; DE OLIVEIRA, ANA MARIA; TOUYZ, RHIAN M.; TOSTES, RITA C.. Chemerin receptor blockade improves vascular function in diabetic obese mice via redox-sensitive and Akt-dependent pathways. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 315, n. 6, p. H1851-H1860, DEC 2018. (13/08216-2, 15/01630-3, 12/13144-8)

NEVES, KARLA BIANCA; LOBATO, N. S.; CAT, A. NGUYEN DINH; LOPES, R. A. M.; HOOD, K. Y.; OLIVEIRA, A. M.; MONTEZANO, A. C.; TOUYZ, R. M.; TOSTES, R. C.. Chemerin/ChemR23 system plays crucial role upon vascular insulin signaling in db/db mice. FASEB JOURNAL, v. 30, p. 2-pg., 2016-04-01. (15/01630-3, 12/13144-8)