Positive Health Online

Abstract

PASCOAL and COLLEAGUES, 1. Obesity and Comorbidities Research Center, Laboratory of Cell Signaling, University of Campinas, Campinas, SP, 13084-761, Brazil; 2. Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil; 3. Obesity and Comorbidities Research Center, Laboratory of Cell Signaling, University of Campinas, Campinas, SP, 13084-761, Brazil. lavelloso.unicamp@gmail.com evaluated the presence and function of RvD2, a resolvin produced from docosahexaenoic acid, in the hypothalamus of mice which could provide an approach to controlling body mass.

Background

Diet-induced hypothalamic inflammation is an important mechanism leading to dysfunction of neurons involved in controlling body mass. Studies have shown that polyunsaturated fats can reduce hypothalamic inflammation. Here, we evaluated the presence and function of RvD2, a resolvin produced from docosahexaenoic acid, in the hypothalamus of mice.

Methodology

Male Swiss mice were fed either chow or a high-fat diet. RvD2 receptor and synthetic enzymes were evaluated by real-time PCR and immunofluorescence. RvD2 was determined by mass spectrometry. Dietary and pharmacological approaches were used to modulate the RvD2 system in the hypothalamus, and metabolic phenotype consequences were determined.

Results

All enzymes involved in the synthesis of RvD2 were detected in the hypothalamus and were modulated in response to the consumption of dietary saturated fats, 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 fats. The substitution of saturated by polyunsaturated fats in the diet resulted in increased hypothalamic RvD2, which was accompanied by reduced body mass and improved glucose tolerance. 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, intracerebroventricular treatment with RvD2 resulted in reduced adiposity, improved glucose tolerance and increased hypothalamic expression of anti-inflammatory cytokines.

Conclusion

Thus, RvD2 is produced in the hypothalamus, and its receptor and synthetic enzymes are modulated by dietary fats. The improved metabolic outcomes of RvD2 make this substance an attractive approach to treat obesity.

References

Pascoal LB1, Bombassaro B1, Ramalho AF1, Coope A1, Moura RF1, Correa-da-Silva F1, Ignacio-Souza L1, Razolli D1, de Oliveira D2, Catharino R2, Velloso LA3. Resolvin RvD2 reduces hypothalamic inflammation and rescues mice from diet-induced obesity. J Neuroinflammation. 14(1):5. doi: 10.1186/s12974-016-0777-2. Jan 5 2017.