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| Author(s): |
Felipe Corrêa da Silva
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2019-12-17 |
| Examining board members: |
Pedro Manoel Mendes de Moraes Vieira;
Niels Olsen Saraiva Camara;
Licio Augusto Velloso
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| Advisor: | Pedro Manoel Mendes de Moraes Vieira |
| Abstract | |
The molecular mechanisms involved in the genesis of obesity are extremely relevant for prevention and future treatment of metabolic diseases. The systemic metabolic regulation, in mammals, is orchestrated by neurons located in the hypothalamus. These neurons are able to sense and integrate peripheral signals, which inform the organism its nutritional status. The impairment of anorexigenic signals is a multifactorial event and, in diet-induced obesity, is mainly induced by the consumption of saturated fatty acids. Effectively, this impairment is translated into death and malfunctioning of POMC (Pro-opiomelanocortin) expressing neurons, triggered by neuroinflammation. Microglia are resident macrophages in the central nervous system and are directly involved in neuroinflammation. Thereby, microglia activation is an essential hub in the genesis of obesity. Our data show that alpha-melanocyte stimulating hormone (alpha-MSH), a POMC-derived peptide, has immunoregulatory roles. alpha-MSH treatment diminished the expression of proinflammatory cytokines in primary murine microglia cells, in a mechanism dependent of melanocortin receptor 3 ¿ MC3R. Also, alpha-MSH treatment induced the phagocytic activity of microglia, a determinant feature of microglia effector function. We found that the immunoregulatory roles of alpha-MSH in microglia are dependent of immunometabolic regulations, centered in damping of glycolytic profile of microglia, which is a hallmark of proinflammatory macrophages. MC3R expression is induced by proinflammatory stimuli and is also dependent on glycolytic induction. We found that the mitochondrial metabolism is unaltered by alpha-MSH treatment, regardless of LPS activation. Furthermore, acute alpha-MSH administration into the hypothalamus of mice on high fat diet led to reduction of the proinflammatory mediators, as observed in vitro. Thereby alpha-MSH has anti-inflammatory properties, translated into damping of the expression of cytokines in an immunometabolic dependent pathway (AU) | |
| FAPESP's process: | 17/06225-5 - Influence of synthetic ([Nle 4, D-Phe7] -±-MSH on microglia metabolism: possible implications on obesity development |
| Grantee: | Felipe Corrêa da Silva |
| Support Opportunities: | Scholarships in Brazil - Master |