The importance of the action of growth hormone on the hypothalamus NPY/AgRP neurons.

Author(s)

Gisele Cristina Lopes Couto

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2019-04-09

Examining board members

José Donato Júnior; Cecilia Helena de Azevedo Gouveia Ferreira; Maria Tereza Nunes; Patrícia de Oliveira Prada

• Advisor: José Donato Júnior

Abstract

Growth hormone (GH) acts on peripheral tissues and is related to various functions of the organism such as metabolism control, somatic growth and cellular processes. There is evidence that GH may exert effects on the central nervous system (CNS). Neurons co-expressing the neuropeptide Y (NPY) and related protein agouti (AgRP) are located in the ventromedial part of the arcuate nucleus of the hypothalamus (ARH). In order to study the action of GH specifically on NPY/AgRP neurons, we will use the Cre-LoxP system that allows a genetic manipulation in a tissue-specific manner. Thus, we inactivate the GH receptor in NPY/AgRP neurons in female animals (GHR/AgRP KO). It is well established that this population of neurons is known as a potent stimulator of appetite, so we aim to verify if the lack of the GH receptor (GHR) can impact metabolic factors. In the validation of the model we observed that NPY/AgRP neurons are responsive to GH. GHR/AgRP KO females shown no difference in body weight. In addition, no differences were observed in metabolic evaluation, such as glucose tolerance, insulin sensitivity or leptin response. As well as we didn\'t observe significant differences in energy expenditure. When challenged with dietary restriction, GHR/AgRP KO females presented greater difficulty in sustaining glycemia and lost more weight than control females. On the other hand, the counter-regulatory response to hypoglycemia is similar between the GHR/AgRP KO and control animals. Also, when exposed to containment stress, the GHR/AgRP KO females presented similar food consumption to the control animals. A second group was generated with the purpose of analyzing the energy balance and glucose homeostasis during pregnancy and lactation. The groups responded similarly to both energy balance and glycemia. Finally, after the aspects related to energy metabolism, using the three-point flexural test technique, which analyzes parameters related to bone metabolism, we observed that the control and GHR/AgRP KO groups didn\'t present significant differences in the analyzed bone parameters. Our results suggest that GH exerts an effect on the metabolism via NPY/AgRP neurons only during situations of chronic stress such as food deprivation. (AU)

• FAPESP's process: 17/04006-4 - The importance of growth hormone's action on NPY/AgRP neurons
• Grantee: Gisele Cristina Lopes Couto Spiri
• Support Opportunities: Scholarships in Brazil - Master