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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 type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): May 02, 2016
Effective date (End): May 01, 2017
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Licio Augusto Velloso
Grantee:Roberta Haddad Tóvolli
Supervisor abroad: Marc Claret
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Local de pesquisa : 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
(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)
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.; BEIROA, DANIEL; SANCHEZ-REBORDELO, ESTRELLA; SENRA, ANA; MALAGON, JOSE A.; VALERIO, PATRICIA; FONDEVILA, MARCOS F.; FERNO, JOHAN; MALAGON, MARIA M.; CONTRERAS, RAIAN; PFLUGER, PAUL; BRUENING, JENS C.; YEO, GILES; TSCHOEP, MATTHIAS; DIEGUEZ, CARLOS; LOPEZ, MIGUEL; CLARET, MARC; KLOPPENBURG, PETER; SABIO, GUADALUPE; NOGUEIRAS, RUBEN. p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1. NATURE COMMUNICATIONS, v. 9, AUG 24 2018. Web of Science Citations: 5.
RAMIREZ, SARA; GOMEZ-VALADES, ALICIA G.; SCHNEEBERGER, MARC; VARELA, LUIS; HADDAD-TOVOLLI, ROBERTA; ALTIRRIBA, JORDI; NOGUERA, EDUARD; DROUGARD, ANNE; FLORES-MARTINEZ, ALVARO; IMBERNON, MONICA; CHIVITE, INIGO; POZO, MACARENA; VIDAL-ITRIAGO, ANDRES; GARCIA, AINHOA; CERVANTES, SARA; GASA, ROSA; NOGUEIRAS, RUBEN; GAMA-PEREZ, PAU; GARCIA-ROVES, PABLO M.; CANO, DAVID A.; KNAUF, CLAUDE; SERVITJA, JOAN-MARC; HORVATH, TAMAS L.; GOMIS, RAMON; ZORZANO, ANTONIO; CLARET, MARC. 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. Web of Science Citations: 25.
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. Web of Science Citations: 22.

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