INVESTIGATION OF SATURATED FAT ACID AND HIGH-FAT DIET EXPOSURE ON CB2 RECEPTOR SIGNALING IN MICROGLIAL CELLS.

• Grant number: 12/18179-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2013
• End date: January 31, 2017
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Lucila Leico Kagohara Elias
• Grantee: Rodrigo César Rorato
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 14/20704-5 - Role of hypothalamic AgRP/NPY neurons in the Hypothalamus-Pituitary-Thyroid axis control in fed and fasted mice, BE.EP.PD

Abstract

There are studies showing that obesity is related to low grade inflammation, which is associated with a decrease in neuronal responsiveness to leptin in the hypothalamus. In addition, an increased endocannabinoid (Ecs) tonus in the hypothalamus, mediated by CB1 receptor signaling, also contributes to obesity by increasing orexigenic hypothalamic neuronal activity. It was also observed an activation of hypothalamic microglia, the major brain cell type implicated in the increase of pro-inflammatory cytokines. On the other hand, the inflammatory status per se also induces synthesis of anti inflammatory modulators, preventing an inappropriate increase in the activity of the immune system; among these modulators are the Ecs acting through CB2 receptors. However, the anti inflammatory effects of Ecs on microglia cells through CB2 signaling could be impaired by hypothalamic inflammation, since desensitization of CB2 signaling was demonstrated, via receptor internalization, after prolonged agonist exposure. Therefore, the aim of this study is to investigate the effects of saturated fat acid on CB2 signaling in the microglia. Using in vivo studies, we will also investigate the CB2 signaling in rats with high fat diet induced hypothalamic inflammation. To attain these purposes, we will use ELISA to determine cytokines level in the medium culture, Western blotting to determine the protein levels, immunofluorescence to investigate protein involved with microglia activity and CB2 signaling, as well as, Dagla gene silencing, to verify the role of 2-AG on CB2-mediated anti-inflammatory effects.

Scientific publications

(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)

RORATO, RODRIGO; BORGES, BEATRIZ DE CARVALHO; UCHOA, ERNANE TORRES; ANTUNES-RODRIGUES, JOSE; ELIAS, CAROL FUZETI; KAGOHARA ELIAS, LUCILA LEICO. LPS-Induced Low-Grade Inflammation Increases Hypothalamic JNK Expression and Causes Central Insulin Resistance Irrespective of Body Weight Changes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 7, p. 14-pg., 2017-07-01. (13/09799-1, 12/18179-4)

RORATO, RODRIGO; BORGES, BEATRIZ DE CARVALHO; UCHOA, ERNANE TORRES; ANTUNES-RODRIGUES, JOSE; ELIAS, CAROL FUZETI; KAGOHARA ELIAS, LUCILA LEICO. LPS-Induced Low-Grade Inflammation Increases Hypothalamic JNK Expression and Causes Central Insulin Resistance Irrespective of Body Weight Changes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 7, JUL 2017. (13/09799-1, 12/18179-4)

RIVAS, PRISCILA M. S.; VECHIATO, FERNANDA M. V.; BORGES, BEATRIZ C.; RORATO, RODRIGO; ANTUNES-RODRIGUES, JOSE; ELIAS, LUCILA L. K.. Increase in hypothalamic AMPK phosphorylation induced by prolonged exposure to LPS involves ghrelin and CB1R signaling. Hormones and Behavior, v. 93, p. 166-174, JUL 2017. (13/03915-0, 13/09799-1, 12/18179-4)