Modulation of S6Ks expression in the nervous central system and effects in obesity

Author(s)

Mariana Rosolen Tavares

• Document type: Doctoral Thesis
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2019-09-06

Examining board members

Fernando Moreira Simabuco; Dennys Esper Cintra; Leandro Pereira de Moura; Adelino Sanchéz Ramos da Silva; Rodrigo Ferreira de Moura

• Advisor: Fernando Moreira Simabuco; Marcio Alberto Torsoni

Abstract

Obesity has been considered a worldwide epidemic. In Brazil, more than half of the population is overweighted and obesity values also continue to rise. WHO data are categorical in claiming that obesity is responsible for the development of pathologies, including type II diabetes, cardiovascular disease, stroke, dyslipidemia and some cancers. Therefore, there is a great demand for a better understanding of the biochemical and metabolic processes related to obesity. The mTOR signaling pathway has been associated with the control of the energy balance, functioning as a sensor of the quantity of nutrients available and acting as a signal for the energy expenditure or energy storage. The present work aimed to study the roles of different S6Ks, known effectors of the mTOR pathway, in the central nervous system (CNS) and their consequences for the body energetic homeostasis. Thus, the focus was to characterize and differentiate the S6Ks roles with the modulation of S6Ks expression in the hypothalamus. In order to overexpress the S6Ks isoforms in the mice hypothalamus, adenovirus vectors were used, which were able to perform this function in vitro. The increase in the hypothalamic S6Ks expression decreases food intake and fasting sensitivity of mice, as well as modulated the mRNA expression of AgRP and NPY neuropeptides. On the other hand, they appear to impair peripheral glucose metabolism. A Cre-LoxP approach was used to overexpress p54-S6K2 isoform in AgRP neurons. Data demonstrate a potential role of the S6K2 protein in AgRP neurons, controlling feeding behavior. The present study highlights the important role of the mTOR/S6Ks signaling pathway in metabolic control, necessary for a better understanding of the physiological processes involved in the obesity progression (AU)

• FAPESP's process: 15/24475-3 - Modulation of expression of S6Ks in the central nervous system and its effects in obesity
• Grantee: Mariana Rosolen Tavares
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)