Translatome analysis of mouse POMC neurons and epigenetic analysis of the median eminence BBB in diet-induced obese offspring

• Grant number: 16/01868-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 02, 2016
• End date: May 01, 2017
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Licio Augusto Velloso
• Grantee: Roberta Haddad Tóvolli
• Supervisor: Marc Claret
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain
• Associated to the scholarship: 15/02913-9 - Structural and molecular analysis of the hypotalamus median eminence of mice born from high fat diet fed mothers, BP.PD

Abstract

The hypothalamus is a region of the brain responsible for the maintenance of the internal milieu and the energy balance of the organism. Specific neuronal populations control the balance between hungry and satiety. Pomc neurons activation promotes satiety and increase energy expenditure. A deeper comprehension of its function can bring new perspectives for the treatment of obesity. In addition, the hypothalamus provides hormones to the pituitary through the median eminence (ME) in a region lacking the blood brain barrier (BBB). Hypothalamic developmental alterations can cause pathological conditions in the adult (including high blood pressure and obesity) and the study of its alterations in an obesogenic fetal environment can improve the alarming cases of childhood obesity. In this context, the objectives for the research period abroad are to investigate and compare the translatome of Pomc neurons using a RiboTag approach in lean and obese female mice and to continue analyzing the effects of obesity in the programming of hypothalamic neurons and the development of the BBB structure during development and early life. To achieve these goals, the project plans to cross RiboTag mouse with a Pomc-Cre line and subsequently analyze the active protein translation taking place in active Pomc neurons of obese and lean mouse offspring. In addition, the histological and molecular alterations observed in the patterning, structure and function of the hypothalamic nuclei involved with feeding circuits and the ME and BBB of diet-induced obese mothers offspring will be further characterized by epigenetic mechanisms. (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)

RAMIREZ, SARA; GOMEZ-VALADES, ALICIA G.; SCHNEEBERGER, MARC; VARELA, LUIS; HADDAD-TOVOLLI, ROBERTA; ALTIRRIBA, JORDI; NOGUERA, EDUARD; DROUGARD, ANNE; FLORES-MARTINEZ, ALVARO; IMBERNON, MONICA; et al. Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control. Cell Metabolism, v. 25, n. 6, p. 1390+, JUN 6 2017. (16/01868-2)

QUINONES, MAR; AL-MASSADI, OMAR; FOLGUEIRA, CINTIA; BREMSER, STEPHAN; GALLEGO, ROSALIA; TORRES-LEAL, LEONARDO; HADDAD-TOVOLLI, ROBERTA; GARCIA-CACERES, CRISTINA; HERNANDEZ-BAUTISTA, RENE; LAM, BRIAN Y. H.; et al. p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1. NATURE COMMUNICATIONS, v. 9, AUG 24 2018. (16/01868-2)

HADDAD-TOVOLLI, ROBERTA; DRAGANO, NATHALIA R. V.; RAMALHO, ALBINA F. S.; VELLOSO, LICIO A.. Development and Function of the Blood-Brain Barrier in the Context of Metabolic Control. FRONTIERS IN NEUROSCIENCE, v. 11, APR 21 2017. (15/50278-0, 15/02913-9, 14/26942-5, 16/01868-2, 13/07607-8)

HADDAD-TOVOLLI, ROBERTA; ALTIRRIBA, JORDI; OBRI, ARNAUD; EYRE SANCHEZ, ELENA; CHIVITE, INIGO; MILA-GUASCH, MARIA; RAMIREZ, SARA; GOMEZ-VALADES, ALICIA G.; POZO, MACARENA; BURGUET, JASMINE; et al. Pro-opiomelanocortin (POMC) neuron translatome signatures underlying obesogenic gestational malprogramming in mice. MOLECULAR METABOLISM, v. 36, p. 11-pg., 2020-06-01. (16/01868-2)