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Orexin participation in the interaction between hunger and reward control systems in spontaneously lean and obese animals kept with normocaloric diet

Grant number: 16/09270-9
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2017
Effective date (End): December 31, 2017
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Gabriel Forato Anhê
Grantee:Joseane Morari Ricciardi de Aguiar
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

Obesity is a major global health problem. The world´s population has individuals who gain weight at different proportions, even without evident absolute increase in the daily intake amount of fats, which suggests that environmental factors such as non-genetic or epigenetic determinants have a very important significance in the development of this disease.It is known that the hunger is controled through the homeostatic and hedonic systems. The hypothalamus (central control homeostatic system) has an important role in the regulation of energy homeostasis, controlling hunger and satiety, and energy expenditure, through their sensitivity and response to major hunger regulating hormones (ghrelin) and satiety (leptin and insulin). The reward system is also able to respond to these hormones, so that the signal coming from each will influence an increase or decrease in dopamine release, resulting in changes in food intake. However, little is known about the circuits that make up the communication between the homeostatic system and the hedonic system in the control of hunger.Thus, the project aims to evaluate the alterations in the production of neuropeptides and neurotransmitters in spontaneously lean and obese animals kept in normocaloric diet (standard rodent chow). In addition, the study aims to see whether there are metabolic changes in these animals, such as a decrease in sensitivity to insulin, leptin and ghrelin, and verify the existence of neuronal circuits that integrate the major systems that control hunger (homeostatic and reward ). In particular, designed experiments will test the potential correlation between the production of orexin from the lateral hypothalamus and the expression of genes which control the production and release of dopamine in the tegmental ventral area, since some pilot data suggested a possible correlation between an increase in orexin expression in the lateral hypothalamus and the increase in tyrosine hydroxylase in the ventral tegmental area. These data are reinforced by findings described in the literature. (AU)