Evaluation of expression and distribution of Nhlh2 protein in the hypothalamus of animals subjected to high fat diet

• Grant number: 16/00977-2
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2018
• Effective date (End): May 31, 2020
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal researcher: Licio Augusto Velloso
• Grantee: Rodrigo Scarpari Carraro
• Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

In several experimental models of obesity is observed progressive loss of hypothalamic ability to maintain energy homeostasis. This is due to the fact that neurons of the medium-basal hypothalamus nuclei - important in controlling hunger and energy expenditure - develop resistance to the main controlling factors of hunger and thermogenesis and leptin is the most important of these. Studies over the past decade have elucidated some mechanisms responsible for leptin resistance in the hypothalamus during the obesity. Saturated long chain fatty acids present in the diet induces a very early inflammatory response in the hypothalamus, to activate TLR4 receptors and induce inflammation and endoplasmic reticulum stress. One of these hypothalamic neuronal groups produce proopiomelanocortin (POMC) that is cleaved to give rise to ± melanocyte hormone (±-MSH), by protein convertase 1 (PC1 / 3). It is further understood that Nhlh2 controls mRNA expression of the gene PC1 / 3 because it heterodimerize with Stat3 and transcribes more protein convertases and therefore controls the level of all active neuropeptides produced from POMC. Knockout animals of Nhlh2 protein present an obese phenotype, which highlights its potential involvement in the genesis of obesity. In this project we will evaluate the expression and distribution of Nhlh2 protein correlating with inflammation in the hypothalamus of animals subjected to high fat diet. Besides, we will also evaluate whether changes in its pattern of expression can modulate the hypothalamic levels of POMC and its byproducts. The identification of early mechanisms that contribute to the development of hypothalamic dysfunction in obesity may help them to develop more effective preventive approaches for this disease.

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)

CARRARO, RODRIGO S.; NOGUEIRA, GUILHERME A.; SIDARTA-OLIVEIRA, DAVI; GASPAR, RODRIGO S.; DRAGANO, NATHALIA R.; MORARI, JOSEANE; BOBBO, VANESSA C. D.; ARAUJO, ELIANA P.; MENDES, NATALIA F.; ZANESCO, ARIANE M.; et al. Arcuate Nucleus Overexpression of NHLH2 Reduces Body Mass and Attenuates Obesity-Associated Anxiety/ Depression-like Behavior. JOURNAL OF NEUROSCIENCE, v. 41, n. 48, p. 10004-10022, DEC 1 2021. (16/00977-2)