Gene expression and role of plasma concentrations of orexigenic and anorexigenic hormones mediated by diet in obesity of patients with craniopharyngioma

• Grant number: 12/18778-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2013
• End date: October 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Margaret de Castro
• Grantee: Mônica Cristina Nogueira Berbél
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Craniopharyngioma (CF) is a nonglial intracranial tumor derived from a malformation of embryonal tissue, located near the optic chiasm, the pituitary gland, and the hypothalamus. Lesions of hypothalamus or adjacent brain structures by the tumor and/or its treatment are possible pathogenic factors of obesity, which is present in approximately 50% of patients. These lesions can cause changes in hormones such as insulin, leptin, adiponectin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and ghrelin. Ghrelin and its receptor (GHS-R) are expressed in several tissues like stomach, pituitary, hypothalamus and several types of tumors, but there are no studies in CF. Thus, this study aims to investigate, in patients with CF, alterations of orexigenic and anorexigenic hormones, sensations of appetite and expression of genes GHRL and GHS-R and its protein products in the tumor. 15 patients submitted to surgical resection of CF and 15 controls matched by sex, age and Body Mass Index (IMC) will be selected. Basal plasma concentrations of leptin and adiponectin and response of glycemia, insulin, HOMA-IR, CCK, GLP-1, PYY and ghrelin to a test meal with soy protein will be evaluated. In the time of blood collection (-15 to 180 minutes) the participants will answer a validated questionnaire of visual analogue scale about the sensations of hunger, satiety and prospective consumption. Furthermore, the expression of genes GHRL and GHS-R will be evaluated in tissue samples of CF (n=11) and normal pituitaries (n=7) by quantitative real-time PCR and the expression of ghrelin and GHS-R proteins by immunohistochemistry.