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Neuronal autophagy in response to palmitate treatment: crosstalk with microglial cells

Grant number: 17/08151-9
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): September 01, 2017
Effective date (End): December 31, 2017
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal Investigator:Marciane Milanski Ferreira
Grantee:Andressa Reginato
Supervisor: Denise Belsham
Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Research place: University of Toronto (U of T), Canada  
Associated to the scholarship:15/25710-6 - Hypothalamic autophagy evaluation in response to treatment with saturated fatty acid in vitro and in vivo: connections with inflammatory pathways, BP.DR


Energy homeostasis involves a complex balance between the neuroendocrine system, located in the medial basal hypothalamus region of the brain, and signals from peripheral organs being important regulators of this communication. During the development of obesity, this system is often compromised by specific insults, including lipotoxicity and release of inflammatory mediators by glia cells. Based on complex structure of the brain, the development and use of primary cultures, as well as immortalized cell models, are an important strategy to understand the molecular mechanisms involved in communication and signaling between neuron and non-neuronal cells, such as microglia. Recently, we have become interested in the crosstalk between hypothalamic neurons and microglia in response to palmitate treatment in vitro and possible consequences to autophagy modulation. Autophagy is a well-known process that regulates cellular homeostasis by degrading malformed organelles and dysfunctional proteins. Normal autophagic activity is crucial to maintain the functionality of hypothalamic neurons. Our group previously demonstrated that chronic use of a high fat diet (HFD) could reduce hypothalamic autophagy in Swiss mice. Importantly, obese animals exposed to rapamycin, an autophagy inducer, had cellular homeostasis restored. Additionally, unpublished data from our laboratory has demonstrated that palmitate treatment induced autophagy flux measured by flow cytometry in a hypothalamic cell line GT1-7. Therefore, in this study we aim to assess autophagy modulation using neuronal and microglia primary culture, as well as feeding-related hypothalamic and microglial cell lines, submitted to palmitate treatment to understand if hypothalamic autophagy downregulation is closely related to intercommunication between these cell populations. These methodological approaches will contribute to the identification of autophagic mechanisms and if palmitate can affect neuronal autophagy flux independent of external afferent connections. We also intend to learn how to cultivate neuronal and microglia cells using a defined co-culture system, as autophagy flux may be dependent on soluble mediators that are released with the contact between these two cell types. Understanding the mechanisms involved in hypothalamic autophagy downregulation triggered by diet is crucial for the advancement of current knowledge. This way it is possible to contribute with the development of obesity-directed therapeutics to control the epidemic of co-morbidities associated with this disease. (AU)

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