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Characterization of the role of the GPR40 receptor in the modulation of precursors of POMC neurons in the adult hypothalamus and its influence on the control of energy homeostasis

Grant number: 18/01360-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2018
Effective date (End): June 30, 2019
Field of knowledge:Biological Sciences - Physiology
Cooperation agreement: Innovation Fund Denmark
Principal Investigator:Licio Augusto Velloso
Grantee:Daiane Fátima Engel
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:15/50278-0 - Anti-obesity effects of nutrients by hypothalamic FFA1 and FFA4 activation, AP.TEM

Abstract

Several studies using experimental models of obesity induced by high fat diet describe functional changes in the hypothalamus, central structure of regulation of the balance between caloric intake and energy expenditure. Among these alterations are apoptosis of neurons in the arched nucleus (ARC) region and reduction in the expression of anorexigenic neuropeptide pro-piolemolanocortin (POMC), suggesting that this population of neurons is the most affected [Moraes et al., PLoS ONE, 2009 (4): e5045]. On the other hand, under physiological conditions, postnatal neurogenesis seems to contribute to the maintenance of the number of POMC + neurons, influencing the control of energy homeostasis. However, this plasticity may be impaired by exposure to a high fat diet, while a diet containing high unsaturated fatty acids (PUFAs), which is associated with an improvement in the obesity phenotype, increases the number of neuronal precursors in the resulting hypothalamus in a greater number of POMC + neurons. The pro-neurogenic effect of the PUFA-rich diet appears to involve GPR40 receptor activation, which also reduces diet-induced weight gain and increases POMC expression [Nascimento et al., Diabetes 2016; 65: 673-6862; Dragano et al., J Neuroinflammation, 2017; 14:91]. In this sense, we hypothesized that the GPR40 receptor represents a potential target in the modulation of postnatal hypothalamic neuroplasticity related to energy homeostasis control. First, we will characterize the precursor cell subtypes of POMC neurons in ARC of adult mice. In the second and main step, we intend to evaluate the involvement of the GPR40 receptor in the maintenance of the proliferative niche and in the definition of the precursor phenotype. Finally, we will characterize the response of precursors (proliferation and differentiation) to stimulation by PUFAs and exposure to a high fat diet. This study will contribute to the understanding of neurogenesis in the adult hypothalamus and how this process can be affected in obesity. (AU)