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| Author(s): |
Lívia Aparecida Davila Bitencourt Pascoal Biazzo
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: | 2016-02-24 |
| Examining board members: |
Licio Augusto Velloso;
Lucila Leico Kagohara Elias;
Emerielle Cristine Vanzela;
Silvana Bordin;
Hosana Gomes Rodrigues
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| Advisor: | Licio Augusto Velloso |
| Abstract | |
Diet-induced hypothalamic inflammation has emerged as an important mechanism leading to the dysfunction of neurons involved in the control of food intake and energy expenditure. A number of pharmacological and genetic approaches that reduce inflammation in the hypothalamus can attenuate the obese and metabolic phenotypes associated with the excessive consumption of dietary fats. Recent studies have shown that polyunsaturated fatty acids can also reduce hypothalamic inflammation. Here, we evaluated the presence and function of RvD2, a resolvin produced from docosahexaenoic acid, in the hypothalamus of obese mice. All enzymes involved in the synthesis of RvD2 were detected in the hypothalamus and were modulated in response to the consumption of dietary fat leading to a reduction of hypothalamic RvD2. GPR18, the receptor for RvD2, which was detected in POMC and NPY neurons, was also modulated by dietary fat. The substitution of saturated by polyunsaturated fatty acids in the diet resulted in increased hypothalamic RvD2, which was accompanied by reduced body mass and improved glucose tolerance. In addition, the intracerebroventricular treatment with docosahexaenoic acid resulted in increased expression of the RvD2 synthetic enzymes, increased expression of anti-inflammatory cytokines and improved metabolic phenotype. Finally, the intracerebroventricular treatment with exogenous RvD2 resulted in reduced adiposity, improved glucose tolerance and increased hypothalamic expression of anti-inflammatory cytokines. In conclusion, RvD2 is produced in the hypothalamus and its receptor and synthetic enzymes are modulated by dietary fat. The improved metabolic outcomes of exogenous RvD2, places this substance as an attractive approach to treat obesity and its comorbidities (AU) | |