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| Author(s): |
Alexandre Moura Assis
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2021-05-19 |
| Examining board members: |
Licio Augusto Velloso;
Eduardo Rochete Ropelle;
Leticia Ignácio de Souza Zimmermann;
Aparecida Emiko Hirata;
Egberto Gaspar de Moura
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| Advisor: | Licio Augusto Velloso |
| Abstract | |
The hypothalamus integrates peripheral signals to a complex neural circuit that controls feeding and energy expenditure. The consumption of high-fat diet triggers an inflammatory response in the hypothalamus and promotes loss of nutrient sensing and apoptosis of POMC neurons after long-term high-fat diet feeding. Here, we investigated the role of TRIL, an acessory protein of TLR4, in the diet-induced hypothalamic inflammation and POMC neuronal function. We showed that TRIL is predominantly expressed in POMC neurons. After the knockdown of TRIL in the arcuate nucleus of the hypothalamus, there was a reduction in hypothalamic inflammation, improved systemic glucose tolerance and protection against diet-induced obesity. The POMC-specific knowckdown of TRIL using Cre-dependent adeno-associated virus promoted body mass reduction and enhanced leptin signaling. Glucose sensitivity is pivotal for the post-prandial activation and apetite-suppressant effects of POMC neurons. In the second part of this Thesis, we analyzed a putative role for PPAR? as an indirect regulator of POMC neurons. CRISPR-Cas9-mediated deletion of PPAR? in POMC neurons was not sufficient to alter glucose and leptin sensitivity, but reduced glucose intolarance in obese mice. In this Thesis, we evaluated two mechanisms potentially involved in hypothalamic dysfunction in obesity and metabolic disorders. Altogether, our results show that TRIL is involved in the development of diet-induced hypothalamic inflammation whereas POMC PPAR? is involved in the hypothalamic regulation of systemic glucose tolerance (AU) | |
| FAPESP's process: | 16/01245-5 - Evaluation of the involvement of TRIL in inflammation and apoptosis of POMC neurons in the hypothalamus of obese mice |
| Grantee: | Alexandre Moura Assis |
| Support Opportunities: | Scholarships in Brazil - Doctorate |