Effects of the adipokine Chemerin on the Responsiveness to Insulin Mesenteric Arteries of Mice

• Grant number: 12/13144-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2012
• Effective date (End): July 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Ana Maria de Oliveira
• Grantee: Karla Bianca Neves
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 15/01630-3 - Role of chemerin/ChemR23 system on insulin signalling in adipocytes and arteries of db/db mice, BE.EP.DR

Abstract

The adipokine chemerin is constitutive, which is extremely important to understand the biological effects in non-pathological conditions, although in obesity is observed where hypertrophy and hyperplasia of adipocytes and an increase in synthesis and release of adipokines, with this condition associated with insulin resistance and endothelial dysfunction. Hardly know the effects of adipokine chemerin on vascular function. Whereas chemerin has been associated with key aspects of the metabolic syndrome and that studies have suggested that proinflammatory adipokines have important role in controlling insulin sensitivity, this study will assess the biological activity of this adipokine on cell responsiveness to insulin non-obese animals. Although it is well established that the metabolic consequences of insulin resistance alone is sufficient to induce changes in the cardiovascular system, the local actions of insulin on the blood vessels are also very relevant. Insulin plays an important role in maintaining the quiescent state of the vascular smooth muscle cells (VSMCs) through of the phosphatidylinositol-3 kinase (PI3K) activation, but also promotes the migration of VSMCs through of the MAPKs. Considering the role of insulin in the control of vascular function under physiological conditions and their ability to maintain VSMCs into quiescence and proinflammatory adipokines modulate cell proliferation as much insulin sensitivity, the hypothesis of this study is that decreases adipokine chemerin the sensitivity of mesenteric arteries to the actions of insulin and increases the proliferation/migration of VSMCs. Our specific objectives include to determine: 1) whether chemerin alter the vasodilator response promoted by insulin, 2) whether these changes are mediated by changes in pathways involved in the production and/or release of NO, ET-1 and/or reactive oxygen species (ROS) by vascular endothelium, and 3) whether chemerin alter the effects promoted by insulin on VSMCs, 4) the role of two major signaling pathways that are activated by insulin in the effects promoted by chemerin: IRS/PI3K and MAPKs pathways. We intend this study to understand the effects produced by this adipokine in vascular responsiveness to insulin and also to understand the mechanisms by which it promotes such actions. Our studies contribute to a better understanding of the role of factors released by visceral adipose tissue on vascular function and, consequently, on the vascular lesions in obesity and associated diseases, such as type 2 diabetes, hypertension and cardiovascular disease.

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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

NEVES, Karla Bianca. Role of chemerin/ChemR23 system on vascular insulin signaling in C57BL/6J and db/db mice. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.