Resolvin RvD2 reduces hypothalamic inflammation and rescues mice from diet-induced obesity

Abstract

BackgroundDiet-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.MethodsMale 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.ResultsAll 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.ConclusionsThus, 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0777-2) contains supplementary material, which is available to authorized users.

Resolvin D2 protects against cerebral ischemia/reperfusion injury in rats

“…Furthermore, LOX played a critical role in the conversion of DHA into RvD2: 12/15-lox could promote DHA conversion to 17-HDHA, and 17-HDHA then generated 17-HPDHA, which could be metabolized to RvD2 after 5-LOX phosphorylation. A recent study suggested that phosphorylation of 5-LOX at serine 663 could stimulate lipoxin production, which plays a role in the last steps of RvD2 synthesis [ 32 ]. In this study, we found that the level of p5-LOX was significantly decreased after MCAO/R, leading to the metabolic failure of ω-3 fatty acids.…”

A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice

“…IL-6 can increase IL-10, IL-1 receptor antagonist, and soluble TNF receptors (Petersen & Pedersen, 2005;Steensberg, Fischer, Keller, Moller, & Pedersen, 2003). Also, IL-6 appears to have an influence on the regulation of appetite, energy expenditure and body composition (Pascoal et al, 2017;Ropelle et al, 2010). Matthews et al (2010) found that IL-6-deficient mice (IL-6 −/− ) consuming a normal diet showed obesity, liver inflammation and insulin resistance compared to control animals (IL6 +/+ ), without a change in food consumption.…”

Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors

“…In addition, RvD2 enhanced endothelial cell migration in a Rac-dependent manner, via DRV2/GPR18, and Gpr18 -deficient mice had an endogenous defect in perfusion recovery following hind limb ischemia (Zhang et al, 2016). RvD2 and its receptor reduce neuroinflammation that impacts systemic obesity (Pascoal et al, 2017). …”