THE REGULATION OF INSULIN AND LEPTIN SIGNALING IN THE STRIATUM: EFFECTS ON FOOD INTAKE, INFLAMATORY PATHWAY AND ENDOPLASMATIC RETICULUM STRESS

• Grant number: 11/15013-5
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2012
• Effective date (End): July 31, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Patrícia de Oliveira Prada
• Grantee: Gisele de Castro
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

Obesity is an exponentially growing disease. Therefore, the study of molecular mechanisms related to the obesity development is extremely relevant nowadays. Recent evidence suggests that insulin and leptin act in the regions of dopaminergic system of reward, beyond the hypothalamus. The striatum is part of this system and was regarded as an important area for regulation of food intake. However there are no studies demonstrating that insulin and leptin signaling are involved in the regulation of food intake in this region. In this sense, the first objective of the study is to investigate the expression / level of phosphorylation of proteins of the signaling pathway of insulin and leptin, and the modulation of food intake after stimulation with these hormones in the striatum region in control animals. As a complement, the second objective of the study is to investigate whether the pharmacological blockade of the PI3K pathway with (LY24002) or JAK2 (AG490) in the striatum may alter food intake in response to insulin or leptin in the control animals. The high-fat diet consumption has been associated with insulin resistance in the hypothalamus through activation of the inflammatory and stress of the endoplasmatic reticulum. Therefore, the third objective is to investigate the expression / level of phosphorylation of proteins of the signaling pathway of insulin and leptin, and the modulation of food intake induced by these hormones in the region of the striatum in animals with diet-induced obesity. If there is reduction in the activation of proteins of the signaling pathway of insulin and leptin in obese animals striatum, we will investigate the fourth goal of the study, the inflammatory pathway IKK / IKB / NFkB and stress of the ER are altered in striatum of obese animals.

Academic Publications

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

CASTRO, Gisele de. Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in amygdala of rats. 2013. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas Limeira, SP.